Berkeley biologists have a new tool to track and videotape cells moving about inside living tissue.
Called two-photon laser-scanning microscopy, it has revealed, for example, the dramatic difference between the random
wanderings of immature T cells and the goal-oriented, beeline movement of activated T cells.
"This is the first time anybody has quantitated four-dimensional data - spatial and time data - to get a picture of
long-range cell migrations through tissue," said immunologist Ellen Robey, professor of immunology at the University of
California, Berkeley. "The ability to directly visualize cells in living tissues has changed the way immunologists think
about how cells explore their environment, how they signal to each other, and how they migrate."
Robey and post-doctoral colleague Colleen Witt are among a handful of researchers using two-photon imaging to obtain
real-time images of cells throughout the top half-millimeter of a living organ, not just on the surface of tissue or within a
slice.
"In our earlier studies (published in Science) we could see cells getting together, presumably signaling one another. In our
current work, we observe cells that we believe have already gotten a signal beelining away," Robey said of her studies in the
thymus, the immune system gland that weans baby T cells into activated helper, or CD4, cells and killer, or CD8, cells primed
for combat with viral invaders. "We were surprised by how rapidly and directly the cells move to their final destination."
The technique could allow researchers in many fields of biology to track migrating cells, which biologists have discovered
are common in many types of tissue, ranging from nerves to lymph nodes. To date, such long-range migrations have been
inferred from observations of chemically fixed tissue at different stages of development.
"Two-photon imaging is going to change literally forever the way that we do biological science," said Witt, a developmental
immunologist. "In the past, we'd take organs out, smush them up and basically do biochemistry in test tubes, or watch their
behavior in a single layer of cells. It's an imaging revolution to be able to go into the native environment while keeping
the intact organ alive and make movies of migrating cells."
With two-photon imaging, Witt and Robey identified thymus cells they dubbed beeliners moving nearly two centimeters - almost
an inch - per hour, which is fast in the realm of cell movement. They think that these are cells that have received a signal
committing them to be either a helper T cell - which aids other immune cells in fighting infections - or a killer T cell that
seeks and destroys cells infected with virus.
On the other hand, uncommitted or immature T cells, what they call meanderers, wander slowly and apparently randomly around
the outer layer, or cortex, of the thymus, perhaps in search of that life-altering signal.
Robey hopes to use two-photon imaging to investigate the signals responsible for changing these meanderers into purposeful
beeliners that immediately leave the cortex for the interior medulla of the thymus.
"We're now at the point with this technology that we can begin to look at the movement of signaling molecules within the
cells," she said.
Robey, with another colleague, Philippe Bousso, last year published a review in the journal Immunity describing the
contributions two-photo imaging has made to the field. Robey and Witt publish their current study in the May 3 issue of the
Public Library Of Science-Biology.
Two-photon imaging is a variation on the standard technique of labeling cells with fluorescent dye and then hitting them with
a laser that makes the dye glow and the cells light up. A certain energy or color of laser light is needed to make the dye,
in this case green fluorescent protein, glow. But high-frequency, short-wavelength visible light, like green, doesn't
penetrate tissue as deeply as longer, redder wavelengths.
The idea behind two-photon imaging is that if you hit a dye molecule in a short period of time with two photons of light,
each photon half the energy needed to excite it, the dye can absorb them together and then fluoresce. The less energetic,
long-wavelength photons will go deeper into the tissue, cause less damage and scatter less, Robey said, essentially
illuminating slices through the tissue that can be sharply imaged and stacked to produce a 3-D image of the cells in real
time. The system they use employs an infrared laser emitting short intense pulses of 920 nanometer-wavelength light.
In the thymus, it's possible to view cells 400 microns inside the cortex, which is about 4/10 of a millimeter or more than a
hundredth of an inch deep. In the current study, Witt limited her viewing to about 200 microns, though she says in some
tissues less dense than the thymus, light could penetrate nearly a millimeter - deep enough to probe cell activity in most
tissues.
Witt pointed out that obtaining a movie of cell movement is just the beginning. The human eye and brain can't pick out
patterns of movement easily, so statistical techniques are needed to identify cells with different patterns of movement.
As an immunologist, Robey focuses on the lives of T cells produced in the thymus and distributed via the bloodstream to the
lymph nodes, whence they move into the body's tissues. Her first use of two-photon imaging three years ago surprised her and
many immunologists because it showed that thymocytes or immature T cells were highly mobile, traveling thousands of microns
in an hour as they explore the thymus.
The new experiments, conducted primarily by Witt, suggest that this exploration probably is a search for a signal that will
decide the cell's fate. In their experiments on one lobe of the mouse thymus, in fact, Witt and her colleagues saw cells,
possibly those that have made a decision on their fate, halt their wanderings and make a beeline out of the cortex to the
medulla, something immature T cells can't do.
The scenario they've reconstructed from the video and mathematical analysis starts with immature T cells moving out of the
center of the thymus, the medulla, to the very outside edge of the cortex, where they proliferate and fill up the cortex. At
this point, Witt said, they undergo the first of two tests to see if their surface receptors (called T cell receptors) work
properly.
Once they pass that test, they start wandering around in the cortex looking for the second test, which is to bind precisely
to a protein called the major histocompatibility complex (MHC). These cells, the researchers think, are the meanderers. Only
about one percent of thymocytes pass both tests, but Witt and Robey think that those that do are the ones they see beelining
out of the cortex into the medulla to begin their two-week education to distinguish "self" from "non-self" invader.
"To pass into the medulla they have to pass a screening test called positive selection," Witt said. "Once they do, the cells
move very directly at a very fast speed inward toward the medulla, adopting a polarized shape characteristic of migrating
cells."
While Witt and Robey continue their two-photon imaging studies of thymus cells and lymph cells, Witt is trying to encourage
the technology's use in biology generally.
"Immunology is just one example of a subdiscipline of biology that stands to benefit enormously from our new ability to see
in four-dimensions - in 3-D in real time. It opens an entirely different universe to us," Witt said.
Coauthors with Witt and Robey are Arup Chakraborty, UC Berkeley professor of chemistry; Subhadip Raychaudhuri, formerly of UC
Berkeley's chemistry department but now with the Department of Biomedical Engineering at UC Davis; and Brian Schaefer of the
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Md.
The work was supported by grants from the National Institutes of Health.
Contact: Robert Sanders
rsandersberkeley
510-643-6998
University of California - Berkeley
berkeley
четверг, 26 мая 2011 г.
Nobel Prizes Won By Two More American Cancer Society Researchers
Two of the three scientists receiving the 2007 Nobel Prize for Physiology or Medicine received funding from the American Cancer Society early in their careers, bringing to 42 the number of Nobel Laureates among the Society's funded researchers.
Former grantees Mario R. Capecchi, Ph.D. of the University of Utah and Oliver Smithies, Ph.D., of the University of North Carolina are co-winners along with Sir Martin J. Evans of Cardiff University in Wales of the 2007 Nobel Prize in Physiology or Medicine for their groundbreaking discoveries that led to a technology known as gene targeting. Their work enabled scientists to develop targeted "gene knockout" mouse models that allows the study of specific genes involved in cancer, as well as in other diseases.
Like many Society-funded researchers, Drs. Capecchi and Smithies received American Cancer Society grants early in their careers, when funding is particularly hard to get. Dr. Capecchi received a four-year Faculty Research Award (FRA) from the American Cancer Society beginning July 1, 1974. Dr. Smithies received funds for an American Cancer Society Project Grant from July 1, 1974 -- December 31, 1976.
"Throughout its more than 60-year history, the American Cancer Society's research department has recognized the importance of funding promising grants by scientists whose careers are in their infancy," said John R. Seffrin, Ph.D., national chief executive officer of the American Cancer Society. "In just the past four years, seven Society-funded researchers have won the Nobel Prize, a remarkable achievement that is unmatched in the non-profit sector. We congratulate these researchers for receiving this proud honor, which stands as strong evidence of the strength of the Society's peer-review process and the credibility of its research grant program."
The American Cancer Society is dedicated to eliminating cancer as a major health problem by saving lives, diminishing suffering and preventing cancer through research, education, advocacy and service. Founded in 1913 and with national headquarters in Atlanta, the Society has 13 regional Divisions and local offices in 3,400 communities, involving millions of volunteers across the United States. For more information visit cancer/.
Source: David Sampson
American Cancer Society
Former grantees Mario R. Capecchi, Ph.D. of the University of Utah and Oliver Smithies, Ph.D., of the University of North Carolina are co-winners along with Sir Martin J. Evans of Cardiff University in Wales of the 2007 Nobel Prize in Physiology or Medicine for their groundbreaking discoveries that led to a technology known as gene targeting. Their work enabled scientists to develop targeted "gene knockout" mouse models that allows the study of specific genes involved in cancer, as well as in other diseases.
Like many Society-funded researchers, Drs. Capecchi and Smithies received American Cancer Society grants early in their careers, when funding is particularly hard to get. Dr. Capecchi received a four-year Faculty Research Award (FRA) from the American Cancer Society beginning July 1, 1974. Dr. Smithies received funds for an American Cancer Society Project Grant from July 1, 1974 -- December 31, 1976.
"Throughout its more than 60-year history, the American Cancer Society's research department has recognized the importance of funding promising grants by scientists whose careers are in their infancy," said John R. Seffrin, Ph.D., national chief executive officer of the American Cancer Society. "In just the past four years, seven Society-funded researchers have won the Nobel Prize, a remarkable achievement that is unmatched in the non-profit sector. We congratulate these researchers for receiving this proud honor, which stands as strong evidence of the strength of the Society's peer-review process and the credibility of its research grant program."
The American Cancer Society is dedicated to eliminating cancer as a major health problem by saving lives, diminishing suffering and preventing cancer through research, education, advocacy and service. Founded in 1913 and with national headquarters in Atlanta, the Society has 13 regional Divisions and local offices in 3,400 communities, involving millions of volunteers across the United States. For more information visit cancer/.
Source: David Sampson
American Cancer Society
Normal Adult Blood Can Generate Pluripotent Stem Cells, Study Reports
In findings likely to make it easier and faster for stem cell biologists to generate patient-specific embryonic-like stem cells, researchers at Children's Hospital Boston have reprogrammed adult blood cells into induced pluripotent stem (iPS) cells.
This advance will further enable scientists to model a patient's disease in a laboratory dish and potentially create healthy cells and tissues that match that patient immunologically. Instead of an invasive skin biopsy, the study shows that the cells can be obtained from the patient during a routine blood draw.
"A simple blood sample by venipuncture can provide adequate cells for reprogramming," said senior author George Daley, MD, Ph.D., a Howard Hughes Medical Institute investigator in Children's Stem Cell Program.
Last year, Daley's team first reported the generation of iPS cells from human blood, but the blood donors in that study had been specially treated with cytokines to mobilize more progenitor cells from the bone marrow. Such treatment often causes side effects, such as flu-like symptoms. "That brings us back to this work," said Yuin-Han "Jon" Loh, Ph.D., lead author and a postdoctoral fellow in the Daley lab. "We asked ourselves if we could reprogram blood cells from a normal donor."
The results, using cells from four healthy, untreated donors, are published in the July 2 Cell Stem Cell. In the same issue, two other research groups, including another Boston area lab, report similar findings.
"The generation of iPS cells from a small amount of peripheral blood collected from non-pretreated donors is an important step," wrote Shinya Yamanaka in an accompanying commentary. "It is reasonable to predict that the field may see a dramatic shift from using skin fibroblasts to peripheral blood as a source of iPS cells in the very near future." (Yamanaka's lab, in Japan, created the first human iPS cells in 2007.)
Embryonic-like iPS cells derived from patients can provide new insights into how diseases develop and what scientists can do to prevent or treat the diseases. Also, any tissue derived from iPS cells would be an immunological match, allowing for rejection-proof cell transplantation. Such advances are likely about 10 to 15 years away, estimates Daley, also a professor of biological chemistry and molecular pharmacology at Harvard Medical School.
iPS cells now mostly come from skin cells (fibroblasts) in a cumbersome process. In contrast, "we can culture iPS cells from blood in two days as opposed to three weeks with skin fibroblasts," Loh said. The process is about ten-fold less efficient, requiring about 1,000 adult blood cells for every one reprogrammed iPS cell, but a small blood draw provides more than enough extra starting cells, Loh says.
Scientifically, one important piece of evidence from the study showed that some of the iPS cells carried telltale genetic rearrangements of receptors of mature T cells. "This indicates that reprogramming does not simply select for pre-existing stem cells in the culture," Daley said.
The team started with blood from four healthy donors including one sample drawn from a colleague in the lab and three samples provided by co-authors at iPierian, a biotechnology company in South San Francisco. In their research, Loh and his colleagues had to develop new ways to grow the cells in suspension, rather than in a lab dish. They also had to develop a new technique to infect the cells with the viruses that carry the four genetic reprogramming factors into the adult cells.
"Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture," the authors write in their paper. "Reprogramming from blood cells thus represents a fast, safe, and efficient way of generating patient-specific iPSCs."
Funding: National Institutes of Health; Howard Hughes Medical Institute; Systems-based Consortium for Organ Design & Engineering; Agency of Science, Technology, and Research and the Institute of Medical Biology, Singapore.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School.
Source: Children's Hospital Boston
This advance will further enable scientists to model a patient's disease in a laboratory dish and potentially create healthy cells and tissues that match that patient immunologically. Instead of an invasive skin biopsy, the study shows that the cells can be obtained from the patient during a routine blood draw.
"A simple blood sample by venipuncture can provide adequate cells for reprogramming," said senior author George Daley, MD, Ph.D., a Howard Hughes Medical Institute investigator in Children's Stem Cell Program.
Last year, Daley's team first reported the generation of iPS cells from human blood, but the blood donors in that study had been specially treated with cytokines to mobilize more progenitor cells from the bone marrow. Such treatment often causes side effects, such as flu-like symptoms. "That brings us back to this work," said Yuin-Han "Jon" Loh, Ph.D., lead author and a postdoctoral fellow in the Daley lab. "We asked ourselves if we could reprogram blood cells from a normal donor."
The results, using cells from four healthy, untreated donors, are published in the July 2 Cell Stem Cell. In the same issue, two other research groups, including another Boston area lab, report similar findings.
"The generation of iPS cells from a small amount of peripheral blood collected from non-pretreated donors is an important step," wrote Shinya Yamanaka in an accompanying commentary. "It is reasonable to predict that the field may see a dramatic shift from using skin fibroblasts to peripheral blood as a source of iPS cells in the very near future." (Yamanaka's lab, in Japan, created the first human iPS cells in 2007.)
Embryonic-like iPS cells derived from patients can provide new insights into how diseases develop and what scientists can do to prevent or treat the diseases. Also, any tissue derived from iPS cells would be an immunological match, allowing for rejection-proof cell transplantation. Such advances are likely about 10 to 15 years away, estimates Daley, also a professor of biological chemistry and molecular pharmacology at Harvard Medical School.
iPS cells now mostly come from skin cells (fibroblasts) in a cumbersome process. In contrast, "we can culture iPS cells from blood in two days as opposed to three weeks with skin fibroblasts," Loh said. The process is about ten-fold less efficient, requiring about 1,000 adult blood cells for every one reprogrammed iPS cell, but a small blood draw provides more than enough extra starting cells, Loh says.
Scientifically, one important piece of evidence from the study showed that some of the iPS cells carried telltale genetic rearrangements of receptors of mature T cells. "This indicates that reprogramming does not simply select for pre-existing stem cells in the culture," Daley said.
The team started with blood from four healthy donors including one sample drawn from a colleague in the lab and three samples provided by co-authors at iPierian, a biotechnology company in South San Francisco. In their research, Loh and his colleagues had to develop new ways to grow the cells in suspension, rather than in a lab dish. They also had to develop a new technique to infect the cells with the viruses that carry the four genetic reprogramming factors into the adult cells.
"Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture," the authors write in their paper. "Reprogramming from blood cells thus represents a fast, safe, and efficient way of generating patient-specific iPSCs."
Funding: National Institutes of Health; Howard Hughes Medical Institute; Systems-based Consortium for Organ Design & Engineering; Agency of Science, Technology, and Research and the Institute of Medical Biology, Singapore.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School.
Source: Children's Hospital Boston
Critical Superparamagnetic/single-domain Grain-sizes In Interacting Magnetite Particles: Implications For Magnetosomes
Magnetotactic bacteria contain chains of magnetically interacting crystals (magnetosome crystals), which they use for navigation (magnetotaxis).
To improve navigation the magnetosome crystals (usually made of iron oxide) should be magnetically stable. Very small particles become magnetically unstable due to thermal excitation. Previous calculations for the stability threshold size not did include the contribution of magnetic interactions.
The inclusion of which, is found to decrease the threshold size, thereby increasing the range of stable magnetic behaviour. We argue that chains of interacting magnetosome crystals found in magnetotactic bacteria have utilized magnetic interactions to improve navigation.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category. The journal also incorporates Interface Focus, a peer-reviewed, themed supplement, each issue of which concentrates on a specific cross-disciplinary subject.
Journal of the Royal Society Interface
To improve navigation the magnetosome crystals (usually made of iron oxide) should be magnetically stable. Very small particles become magnetically unstable due to thermal excitation. Previous calculations for the stability threshold size not did include the contribution of magnetic interactions.
The inclusion of which, is found to decrease the threshold size, thereby increasing the range of stable magnetic behaviour. We argue that chains of interacting magnetosome crystals found in magnetotactic bacteria have utilized magnetic interactions to improve navigation.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category. The journal also incorporates Interface Focus, a peer-reviewed, themed supplement, each issue of which concentrates on a specific cross-disciplinary subject.
Journal of the Royal Society Interface
$1.2 Million Grant For Groundbreaking Approach To Brain Research Received By UT's Valentin Dragoi
An innovative approach to brain research developed by a scientist at The University of Texas Medical School at Houston has been selected for funding by a National Institutes of Health (NIH) initiative designed to support high-impact, medical investigations.
Valentin Dragoi, Ph.D., assistant professor of neurobiology and anatomy at the UT Medical School at Houston, has been awarded a four-year, $1.2 million grant through the initiative called Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA). The project is titled "Real-time population coding underlying behavioral decisions."
His approach to studying the brain could further the understanding of dissociative disorders that affect about one in 20 Americans.
Dragoi focuses on a region of the brain known as the cerebral cortex, which is a slender carpet of nerve cells or neurons that covers the cerebrum and plays a major role in sight, hearing and motor skills.
The brain is amazingly difficult to interpret because of the high degree of interconnectivity among brain networks, Dragoi said. For instance, sensory inputs are successfully processed by neuronal networks in different cortical areas. Each cortical area consists of multiple layers that contain characteristic patterns of connections with other cortical regions.
Whereas previous research has focused on individual neurons, Dragoi proposes to study the signals of populations of neurons in different regions of the cerebral cortex including visual cortex and high-level cortical areas. Tests will be conducted in an animal model.
"Examining how populations of neurons in multiple cortical areas interact to produce behavior may significantly increase our understanding of how neuronal networks operate in both normal and dysfunctional states," he said.
Dragoi said, "We made tremendous progress in understanding the language of individual neurons. Yet, how populations of cells communicate among each other to control behavior is virtually unknown. The new challenge in neuroscience is to decipher the language of populations of brain cells."
During the experiments, large populations of neurons will be recorded simultaneously using multiple, high-density electrode arrays in three key cortical areas involved in perceptual decisions, Dragoi said. "The experiments that we will perform have the potential to provide key insight into the dynamic transformations of the population code during a behavioral task," he said.
"Although the idea that behavior emerges from interactions among neuronal networks is not new, it has never been tested empirically under the framework of population coding," he said.
"The EUREKA award to Valentin Dragoi will be a major boost to his research on understanding the operation of normal and dysfunctional brain cortical neuronal networks and their impact on the decision-making processes of the brain. We can look forward to many significant scientific breakthroughs from this outstanding young scientist," said John H. Byrne, Ph.D., June and Virgil Waggoner Chair and chairman of the Department of Neurobiology and Anatomy at the UT Medical School at Houston
"It is a great honor for him, the department and the University of Texas Health Science Center at Houston. The fact that only a few grants were awarded within the entire National Institutes of Health is an indicator of the competitiveness of our neuroscience research program at the national level," Byrne said.
To receive a EUREKA grant, a research proposal must be linked to the mission of one of the NIH institutes. Dragoi's research is connected to the National Institute of Mental Health.
Valentin Dragoi received his doctorate at Duke University and completed a postdoctoral fellowship at the Massachusetts Institute of Technology. He is a recipient of numerous awards including the James S. McDonnell Award, the Pew Scholar Award and the Merck Award.
Source:
Robert Cahill
University of Texas Health Science Center at Houston
Valentin Dragoi, Ph.D., assistant professor of neurobiology and anatomy at the UT Medical School at Houston, has been awarded a four-year, $1.2 million grant through the initiative called Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA). The project is titled "Real-time population coding underlying behavioral decisions."
His approach to studying the brain could further the understanding of dissociative disorders that affect about one in 20 Americans.
Dragoi focuses on a region of the brain known as the cerebral cortex, which is a slender carpet of nerve cells or neurons that covers the cerebrum and plays a major role in sight, hearing and motor skills.
The brain is amazingly difficult to interpret because of the high degree of interconnectivity among brain networks, Dragoi said. For instance, sensory inputs are successfully processed by neuronal networks in different cortical areas. Each cortical area consists of multiple layers that contain characteristic patterns of connections with other cortical regions.
Whereas previous research has focused on individual neurons, Dragoi proposes to study the signals of populations of neurons in different regions of the cerebral cortex including visual cortex and high-level cortical areas. Tests will be conducted in an animal model.
"Examining how populations of neurons in multiple cortical areas interact to produce behavior may significantly increase our understanding of how neuronal networks operate in both normal and dysfunctional states," he said.
Dragoi said, "We made tremendous progress in understanding the language of individual neurons. Yet, how populations of cells communicate among each other to control behavior is virtually unknown. The new challenge in neuroscience is to decipher the language of populations of brain cells."
During the experiments, large populations of neurons will be recorded simultaneously using multiple, high-density electrode arrays in three key cortical areas involved in perceptual decisions, Dragoi said. "The experiments that we will perform have the potential to provide key insight into the dynamic transformations of the population code during a behavioral task," he said.
"Although the idea that behavior emerges from interactions among neuronal networks is not new, it has never been tested empirically under the framework of population coding," he said.
"The EUREKA award to Valentin Dragoi will be a major boost to his research on understanding the operation of normal and dysfunctional brain cortical neuronal networks and their impact on the decision-making processes of the brain. We can look forward to many significant scientific breakthroughs from this outstanding young scientist," said John H. Byrne, Ph.D., June and Virgil Waggoner Chair and chairman of the Department of Neurobiology and Anatomy at the UT Medical School at Houston
"It is a great honor for him, the department and the University of Texas Health Science Center at Houston. The fact that only a few grants were awarded within the entire National Institutes of Health is an indicator of the competitiveness of our neuroscience research program at the national level," Byrne said.
To receive a EUREKA grant, a research proposal must be linked to the mission of one of the NIH institutes. Dragoi's research is connected to the National Institute of Mental Health.
Valentin Dragoi received his doctorate at Duke University and completed a postdoctoral fellowship at the Massachusetts Institute of Technology. He is a recipient of numerous awards including the James S. McDonnell Award, the Pew Scholar Award and the Merck Award.
Source:
Robert Cahill
University of Texas Health Science Center at Houston
Lyme Disease-Causing Microbes Seen Moving In Ticks
Lyme disease is caused by the microbe Borrelia burgdorferi, which is transmitted to humans from feeding ticks. Justin Radolf and colleagues, at the University of Connecticut Health Center, Farmington, have now visualized the microbe moving through the feeding tick and determined that it has a biphasic mode of dissemination. These data provide new insight into the transmission process, detailed understanding of which is essential if new methods of preventing human infection with the Lyme disease-causing microbe are to be developed.
In this study, the midguts and salivary glands of ticks before, during, and after feeding were isolated, and the live Borrelia burgdorferi microbes imaged in real time. In the first phase of dissemination, replicating microbes formed networks of nonmotile organisms that moved by adhering to the cells lining the tick midgut. In the second phase of dissemination, the microbes became motile invasive organisms that ultimately entered the salivary glands. These data challenge the conventional viewpoint that Lyme disease-causing microbes are always motile within ticks and that this drives their dissemination.
TITLE: Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks
Author: Justin D. Radolf
View this article at: jci/articles/view/39401?key=HnLk45JRxih3aqbS4YCQ
Source: Karen Honey
Journal of Clinical Investigation
In this study, the midguts and salivary glands of ticks before, during, and after feeding were isolated, and the live Borrelia burgdorferi microbes imaged in real time. In the first phase of dissemination, replicating microbes formed networks of nonmotile organisms that moved by adhering to the cells lining the tick midgut. In the second phase of dissemination, the microbes became motile invasive organisms that ultimately entered the salivary glands. These data challenge the conventional viewpoint that Lyme disease-causing microbes are always motile within ticks and that this drives their dissemination.
TITLE: Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks
Author: Justin D. Radolf
View this article at: jci/articles/view/39401?key=HnLk45JRxih3aqbS4YCQ
Source: Karen Honey
Journal of Clinical Investigation
$100,000 Grand Challenges Explorations Grant Received By Monell Center
The Monell Center has announced that it has received a US$100,000 Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation. The grant will support an innovative global health research project conducted by Paul A. S. Breslin, PhD, titled "Taste-Guided Behavior on Mosquitoes Helps Eradicate Malaria."
Dr. Breslin's project is one of 81 grants announced by the Gates Foundation in the second funding round of Grand Challenges Explorations, an initiative to help scientists around the world explore bold and largely unproven ways to improve health in developing countries. The grants were provided to scientists in 17 countries on six continents.
To receive funding, Breslin showed in a two-page application how his idea falls outside current scientific paradigms and might lead to significant advances in global health. The initiative is highly competitive, receiving more than 3,000 proposals in this round.
Breslin's grant focuses on the sense of taste in mosquitoes, with the overall goal of identifying new strategies to reduce transmission of malaria. Taste provides information that regulates whether a substance will be ingested as food or rejected. As such, the final decision of whether or not a mosquito will initiate a meal of human blood depends on how human skin tastes to the mosquito. Currently, little is known about the taste world of mosquitoes. Dr. Breslin proposes that a deeper understanding of mosquito taste will reveal novel approaches to the design of strategies to reduce mosquito-mediated disease transmission. As a first step, the studies funded by the Grand Challenges Explorations grant will assess taste responses of mosquitoes to a range of human skin compounds.
Paul Breslin is a sensory psychobiologist and geneticist at the Monell Chemical Senses Center in Philadelphia. The Grand Challenges Explorations mosquito project is an extension of his longstanding interests in taste and feeding. Breslin's Drosophila Chemosensory Laboratory at Monell uses the fruit fly as a model to understand the relationships between genetics, chemosensation, and feeding. Parallel studies in Breslin's lab address the genetics of taste, smell, and chemical irritation in humans.
"By deterring mosquito tasting on human skin, we can help to stop the transmission of devastating diseases such as malaria," said Breslin. "The Grand Challenges Explorations grant will enable us to find out what it is about humans that mosquitoes find tasty. With that critical piece of information, we can then develop inhibitors to those substances. Once humans no longer taste good to mosquitoes, they will no longer use us as food."
"The winners of these grants are doing truly exciting and innovative work," said Dr. Tachi Yamada, president of the Gates Foundation's Global Health Program. "I'm optimistic that some of these exploratory projects will lead to life-saving breakthroughs for people in the world's poorest countries."
Source:
Leslie Stein
Monell Chemical Senses Center
Dr. Breslin's project is one of 81 grants announced by the Gates Foundation in the second funding round of Grand Challenges Explorations, an initiative to help scientists around the world explore bold and largely unproven ways to improve health in developing countries. The grants were provided to scientists in 17 countries on six continents.
To receive funding, Breslin showed in a two-page application how his idea falls outside current scientific paradigms and might lead to significant advances in global health. The initiative is highly competitive, receiving more than 3,000 proposals in this round.
Breslin's grant focuses on the sense of taste in mosquitoes, with the overall goal of identifying new strategies to reduce transmission of malaria. Taste provides information that regulates whether a substance will be ingested as food or rejected. As such, the final decision of whether or not a mosquito will initiate a meal of human blood depends on how human skin tastes to the mosquito. Currently, little is known about the taste world of mosquitoes. Dr. Breslin proposes that a deeper understanding of mosquito taste will reveal novel approaches to the design of strategies to reduce mosquito-mediated disease transmission. As a first step, the studies funded by the Grand Challenges Explorations grant will assess taste responses of mosquitoes to a range of human skin compounds.
Paul Breslin is a sensory psychobiologist and geneticist at the Monell Chemical Senses Center in Philadelphia. The Grand Challenges Explorations mosquito project is an extension of his longstanding interests in taste and feeding. Breslin's Drosophila Chemosensory Laboratory at Monell uses the fruit fly as a model to understand the relationships between genetics, chemosensation, and feeding. Parallel studies in Breslin's lab address the genetics of taste, smell, and chemical irritation in humans.
"By deterring mosquito tasting on human skin, we can help to stop the transmission of devastating diseases such as malaria," said Breslin. "The Grand Challenges Explorations grant will enable us to find out what it is about humans that mosquitoes find tasty. With that critical piece of information, we can then develop inhibitors to those substances. Once humans no longer taste good to mosquitoes, they will no longer use us as food."
"The winners of these grants are doing truly exciting and innovative work," said Dr. Tachi Yamada, president of the Gates Foundation's Global Health Program. "I'm optimistic that some of these exploratory projects will lead to life-saving breakthroughs for people in the world's poorest countries."
Source:
Leslie Stein
Monell Chemical Senses Center
The Protein ADK Links Epilepsy And Brain Pathology
The brain of individuals who suffer from epilepsy is characterized by astrogliosis, a brain pathology evidenced by a complex series of changes in the morphology and function of brain cells known as astrocytes. Little is known about how astrogliosis relates to the dysfunction of brain cells known as neurons in individuals with epilepsy, but filling in the blanks in our knowledge could lead to new possibilities for therapeutic intervention. A study using mice by Detlev Boison and colleagues at Legacy Clinical Research, Portland, has now identified the protein ADK in astrocytes as a molecular link between astrogliosis and neuronal dysfunction in epilepsy.
The authors observed in a mouse model of epilepsy that ADK upregulation and spontaneous seizures occurred in the region of the brain affected by astrogliosis. In addition, overexpression of ADK in a specific region of the brain triggered seizures in the absence of astrogliosis. Conversely, mice engineered to express less ADK in specific regions of the brain were protected from chemical-induced epilepsy. Furthermore, as ADK-deficient ES cellвЂ"derived implants protected normal mice from chemical-induced astrogliosis, ADK upregulation, and seizures, it was suggested that ADK-based treatment strategies might provide a new approach for the treatment of individuals with epilepsy.
TITLE: Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice
AUTHOR CONTACT:
Detlev Boison
Legacy Clinical Research, Portland, Oregon, USA.
Source: Karen Honey
Journal of Clinical Investigation
The authors observed in a mouse model of epilepsy that ADK upregulation and spontaneous seizures occurred in the region of the brain affected by astrogliosis. In addition, overexpression of ADK in a specific region of the brain triggered seizures in the absence of astrogliosis. Conversely, mice engineered to express less ADK in specific regions of the brain were protected from chemical-induced epilepsy. Furthermore, as ADK-deficient ES cellвЂ"derived implants protected normal mice from chemical-induced astrogliosis, ADK upregulation, and seizures, it was suggested that ADK-based treatment strategies might provide a new approach for the treatment of individuals with epilepsy.
TITLE: Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice
AUTHOR CONTACT:
Detlev Boison
Legacy Clinical Research, Portland, Oregon, USA.
Source: Karen Honey
Journal of Clinical Investigation
Purdue Experts On Pigs And MRSA Infection Say Link Is Highly Speculative
Purdue University experts said a New York Times opinion piece this week that tried to establish pigs as a source of MRSA infection for humans is "highly speculative."
MRSA, (methicillin-resistant Staphylococcus aureus), or antibiotic-resistant staph, can be found anywhere in nature, according to Paul Ebner, a livestock microbiologist. While he said there has been an increase in the number of these infections and that pigs and other animals can be carriers, the vast majority of infections come from skin-to-skin contact with infected humans.
Making assumptions based on limited studies or information is a big jump and there is no proof to link MRSA in humans to pigs and pig operations at this time, said Ching Ching Wu, professor of veterinary pathobiology and head of microbiology in Purdue's Animal Disease and Diagnostic Laboratory. Wu said there is more scientific evidence to support the spread of MRSA among humans and from humans to animals rather than from animals to humans.
A University of Iowa study mentioned in the Times column was a pilot study that looked at only two farms, and only one of them had the organism. Another Dutch study was also inconclusive, according to the Purdue experts.
Both Ebner and Wu said that because MRSA is so prevalent, the best way to avoid infections is to always use proper hygiene.
Ebner, assistant professor of animal sciences, conducts research into microbiology issues associated with livestock, including food safety and human health implications. Wu researches infectious diseases and antimicrobial resistance and is on the U.S. delegation to address antimicrobial resistance in food worldwide.
The March 12 New York Times op-ed by Nicholas Kristof, titled "Our Pigs, Our Food, Our Health," is available here.
Writer: Beth Forbes
Source
Purdue University
MRSA, (methicillin-resistant Staphylococcus aureus), or antibiotic-resistant staph, can be found anywhere in nature, according to Paul Ebner, a livestock microbiologist. While he said there has been an increase in the number of these infections and that pigs and other animals can be carriers, the vast majority of infections come from skin-to-skin contact with infected humans.
Making assumptions based on limited studies or information is a big jump and there is no proof to link MRSA in humans to pigs and pig operations at this time, said Ching Ching Wu, professor of veterinary pathobiology and head of microbiology in Purdue's Animal Disease and Diagnostic Laboratory. Wu said there is more scientific evidence to support the spread of MRSA among humans and from humans to animals rather than from animals to humans.
A University of Iowa study mentioned in the Times column was a pilot study that looked at only two farms, and only one of them had the organism. Another Dutch study was also inconclusive, according to the Purdue experts.
Both Ebner and Wu said that because MRSA is so prevalent, the best way to avoid infections is to always use proper hygiene.
Ebner, assistant professor of animal sciences, conducts research into microbiology issues associated with livestock, including food safety and human health implications. Wu researches infectious diseases and antimicrobial resistance and is on the U.S. delegation to address antimicrobial resistance in food worldwide.
The March 12 New York Times op-ed by Nicholas Kristof, titled "Our Pigs, Our Food, Our Health," is available here.
Writer: Beth Forbes
Source
Purdue University
Recombinant MOG Proteins - New
Expanding on its world-class collection of MOG peptides and assay kits, AnaSpec is pleased to announce the release of 3 MOG recombinant proteins, for human, mouse and rat.
These proteins, with sequences corresponding to human, mouse and rat extracellular domain, together with a 6x His tag were expressed in E. coli and purified from urea denatured bacterial lysate. The molecular weight found in all 3 recombinant proteins was 14.23 kDa. The activity of these proteins was checked for their ability to induce EAE in either mouse (for the human and mouse rMOGs) or rat (for rat rMOG).
About AnaSpec
AnaSpec is a leading provider of integrated proteomics solutions to the world's largest biotech, pharmaceutical, and academic research institutions. With a vision for innovation through synergy, AnaSpec focuses on three core technologies: peptides, detection reagents (including antibodies, dyes, and assay kits), and combinatorial chemistry.
References
1. Linares, D. et.al. Protein Expression and Purif. 34, 249 (2004).
2. Bettadapura, J. et.al. J. Neurochem. 70, 1593 (1998).
3. Oliver, AR. et al J. Immunol. 171, 462 (2003).
4. Von Budingen, H. et.al. J. Clin. Immunol. 21, 155 (2001).
5. Lyons, J. et.al. Eur. J. Immunol. 29, 3432 (1999)
6. Von Budingen, H. et.al. Eur. J. Immunol. 34, 2072 (2004).
AnaSpec
These proteins, with sequences corresponding to human, mouse and rat extracellular domain, together with a 6x His tag were expressed in E. coli and purified from urea denatured bacterial lysate. The molecular weight found in all 3 recombinant proteins was 14.23 kDa. The activity of these proteins was checked for their ability to induce EAE in either mouse (for the human and mouse rMOGs) or rat (for rat rMOG).
About AnaSpec
AnaSpec is a leading provider of integrated proteomics solutions to the world's largest biotech, pharmaceutical, and academic research institutions. With a vision for innovation through synergy, AnaSpec focuses on three core technologies: peptides, detection reagents (including antibodies, dyes, and assay kits), and combinatorial chemistry.
References
1. Linares, D. et.al. Protein Expression and Purif. 34, 249 (2004).
2. Bettadapura, J. et.al. J. Neurochem. 70, 1593 (1998).
3. Oliver, AR. et al J. Immunol. 171, 462 (2003).
4. Von Budingen, H. et.al. J. Clin. Immunol. 21, 155 (2001).
5. Lyons, J. et.al. Eur. J. Immunol. 29, 3432 (1999)
6. Von Budingen, H. et.al. Eur. J. Immunol. 34, 2072 (2004).
AnaSpec
Assessing Visual Requirements For Social-context Dependent Activation Of The Songbird Song System
This study shows that social context-dependent activation in the brain does not depend on simple sensory processes, such a vision, as one might expect.
Instead, we believe that higher order associative processing occurs, where an individual animal may need to know through at least one sensory modality that another individual is present or that the sensory processing is highly indirect.
This was shown in zebra finch males that sang to females, with one eye covered.
In the brain hemisphere where visual information was block, visual and motivation brain areas were affected but the dramatic differences in social context regulation of the song system that controls singing was not.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
Instead, we believe that higher order associative processing occurs, where an individual animal may need to know through at least one sensory modality that another individual is present or that the sensory processing is highly indirect.
This was shown in zebra finch males that sang to females, with one eye covered.
In the brain hemisphere where visual information was block, visual and motivation brain areas were affected but the dramatic differences in social context regulation of the song system that controls singing was not.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
University Of Chicago Awarded Nearly $23M For Translational Research
The National Institutes of Health has awarded one of 12 Clinical and Translational Science Awards (CTSA) for 2007 to a team based at the University of Chicago Medical Center. These awards, together with 12 CTSAs awarded in 2006, form the core of an NIH effort to build a national consortium of select centers that will "transform how clinical and translational research is conducted," ultimately enabling researchers to provide new and better treatments more efficiently and quickly to patients.
To improve human health, according to the NIH's Roadmap for Medical Research, scientific discoveries must be translated into practical applications. Such discoveries typically begin at the bench with basic research -- in which scientists study disease at a molecular or cellular level -- then progress to the clinical level, or the patient's bedside, and ultimately to widespread adoption as standard clinical practice.
This award to the University of Chicago provides more than $22.6 for a series of such translational projects. It will bring together basic scientists from the biological, physical, behavioral and social sciences, physician-scientists from the medical school, and faculty from the schools of public policy, social service administration, and business. And it will put all those researchers in close contact with the residents of the South Side of Chicago.
Together, they will conduct basic, translational and clinical research; speed the transition of new knowledge from laboratory bench to patient bedside; push the boundaries of personalized medicine; and improve the health of the community. "Through collaboration and leadership, these sites are serving as discovery engines that can rapidly translate research into prevention strategies and clinical treatments for the people who need them," said Elias Zerhouni, MD, director of the National Institutes of Health. "The CTSA consortium also represents our investment in the future as it prepares the next generation of clinical researchers to meet tomorrow's health care challenges." The University of Chicago was selected for its expertise in translational research and its eagerness to cross boundaries. The University has a long history of extensive collaborations among faculty from different disciplines, strong and productive relationships with institutional partners such as Argonne National Laboratory and the Illinois Institute of Technology -- which will also be partners in this project -- and robust and expanding community engagement.
"The ambitious, ultimate goals of this program are to train scientists and health care providers at the University and in our community to determine the molecular underpinnings of disease or disease predisposition in any individual patient," said Julian Solway, MD, Walter L. Palmer Distinguished Service Professor of Medicine and Pediatrics and principal investigator for this project.
"We intend to develop, test, implement, and make readily available to residents in our community personalized therapies directed toward those underpinnings, which might be different among individual patients, and to do this in a way that is rigorous, valid, efficient, ethical, and respectful of our community's needs and values."
"The translation of biomedical discovery into effective, deliverable, and personalized therapies for diverse populations with common, complex disorders is a daunting but tremendously important task," said James Madara, MD, Chief Executive Officer of the University of Chicago Medical Center, University Vice President for Medical Affairs, and Dean of the Division of the Biological Sciences and the Pritzker School of Medicine at the University of Chicago.
"Few cures for common health problems have emerged from strategies that ignore personalized needs," Madara said. "We believe this reflects not only the complexity of the disease processes but also the extreme heterogeneity of patient populations and the corresponding heterogeneity of successful approaches for diagnosis and treatment. The many strengths of the investigators and residents within the University of Chicago community encourage us to meet this challenge head on."
One objective of the CTSA program is to eliminate barriers: between academic disciplines, between laboratory and clinical research, and between scientists, doctors and patients. To reach that objective, the program will bring residents of the many diverse neighborhoods surrounding the University into the research process.
The 1.1 million residents of the South Side of Chicago form a diverse but, in many cases, chronically underserved population. The community has high rates of hypertension, diabetes, asthma and other complex diseases. Ten to 15 percent of adults are physically disabled. Fifteen to 20 percent of all births to neighborhood residents are premature. Area residents over age 35 are three times more likely to be hospitalized for complications of diabetes.
Through partnerships between the University and its Medical Center, other health care providers on the South Side -- including Access Community Health Network and Advocate Healthcare -- the CTSA will attempt to overcome these health disparities by improving access to medical care, and raising the standards of care for all those on the South Side.
The University already is home to three separate centers focused on understanding and alleviating health disparities: the NIH-funded Center for Interdisciplinary Health Disparities Research, the CDC-funded Center for Health and the Social Sciences, and the Robert Wood Johnson Foundation-funded Finding Answers: Disparities Research for Change.
"The CTSA grant will enable us to take great strides forward together," said Solway.
The national CTSA initiative grew out of a commitment by the NIH to re-engineer the clinical research enterprise, one of the key objectives of the NIH's "Roadmap." CTSA applicants were encouraged to create an academic home for clinical and translational science.
For this purpose, the University of Chicago created the Institute for Translational Medicine (ITM). Under Solway's direction, the ITM will operate across academic departments to generate new methods, tools and systems of discovery. The ITM will also interface closely with the committee on clinical and translational science, which will offer a novel curriculum in clinical and translational research.
The specific objectives of the ITM are to:
* Prepare physicians and scientists for careers in translational research.
* Create a seamless career path for young faculty seeking translational investigator status.
* Encourage high school, college, and allied health professions students to seek careers in translational research.
* Provide state-of-the-art resources for translational research, including access to expertise n clinical trial design, biostatistics, epidemiology, ethics, informatics, and regulatory issues.
* Provide comprehensive medical ethics training for current and future clinical and translational researchers.
* Provide a "home" for collaboration between departments and cooperating institutions.
* Enhance communication among investigators.
* Define the key genetic determinants of common, complex disorders.
* Utilize a "systems medicine" approach to treat common, complex disease.
The Medical Center is also preparing to launch a multi-faceted Urban Health Initiative (UHI), which will engage the community in developing clinical and community research agendas; involve community organizations in that research; accelerate the translation of health knowledge and expertise into and out of our community; and strive to reduce health disparities.
Source: John Easton
University of Chicago Medical Center
To improve human health, according to the NIH's Roadmap for Medical Research, scientific discoveries must be translated into practical applications. Such discoveries typically begin at the bench with basic research -- in which scientists study disease at a molecular or cellular level -- then progress to the clinical level, or the patient's bedside, and ultimately to widespread adoption as standard clinical practice.
This award to the University of Chicago provides more than $22.6 for a series of such translational projects. It will bring together basic scientists from the biological, physical, behavioral and social sciences, physician-scientists from the medical school, and faculty from the schools of public policy, social service administration, and business. And it will put all those researchers in close contact with the residents of the South Side of Chicago.
Together, they will conduct basic, translational and clinical research; speed the transition of new knowledge from laboratory bench to patient bedside; push the boundaries of personalized medicine; and improve the health of the community. "Through collaboration and leadership, these sites are serving as discovery engines that can rapidly translate research into prevention strategies and clinical treatments for the people who need them," said Elias Zerhouni, MD, director of the National Institutes of Health. "The CTSA consortium also represents our investment in the future as it prepares the next generation of clinical researchers to meet tomorrow's health care challenges." The University of Chicago was selected for its expertise in translational research and its eagerness to cross boundaries. The University has a long history of extensive collaborations among faculty from different disciplines, strong and productive relationships with institutional partners such as Argonne National Laboratory and the Illinois Institute of Technology -- which will also be partners in this project -- and robust and expanding community engagement.
"The ambitious, ultimate goals of this program are to train scientists and health care providers at the University and in our community to determine the molecular underpinnings of disease or disease predisposition in any individual patient," said Julian Solway, MD, Walter L. Palmer Distinguished Service Professor of Medicine and Pediatrics and principal investigator for this project.
"We intend to develop, test, implement, and make readily available to residents in our community personalized therapies directed toward those underpinnings, which might be different among individual patients, and to do this in a way that is rigorous, valid, efficient, ethical, and respectful of our community's needs and values."
"The translation of biomedical discovery into effective, deliverable, and personalized therapies for diverse populations with common, complex disorders is a daunting but tremendously important task," said James Madara, MD, Chief Executive Officer of the University of Chicago Medical Center, University Vice President for Medical Affairs, and Dean of the Division of the Biological Sciences and the Pritzker School of Medicine at the University of Chicago.
"Few cures for common health problems have emerged from strategies that ignore personalized needs," Madara said. "We believe this reflects not only the complexity of the disease processes but also the extreme heterogeneity of patient populations and the corresponding heterogeneity of successful approaches for diagnosis and treatment. The many strengths of the investigators and residents within the University of Chicago community encourage us to meet this challenge head on."
One objective of the CTSA program is to eliminate barriers: between academic disciplines, between laboratory and clinical research, and between scientists, doctors and patients. To reach that objective, the program will bring residents of the many diverse neighborhoods surrounding the University into the research process.
The 1.1 million residents of the South Side of Chicago form a diverse but, in many cases, chronically underserved population. The community has high rates of hypertension, diabetes, asthma and other complex diseases. Ten to 15 percent of adults are physically disabled. Fifteen to 20 percent of all births to neighborhood residents are premature. Area residents over age 35 are three times more likely to be hospitalized for complications of diabetes.
Through partnerships between the University and its Medical Center, other health care providers on the South Side -- including Access Community Health Network and Advocate Healthcare -- the CTSA will attempt to overcome these health disparities by improving access to medical care, and raising the standards of care for all those on the South Side.
The University already is home to three separate centers focused on understanding and alleviating health disparities: the NIH-funded Center for Interdisciplinary Health Disparities Research, the CDC-funded Center for Health and the Social Sciences, and the Robert Wood Johnson Foundation-funded Finding Answers: Disparities Research for Change.
"The CTSA grant will enable us to take great strides forward together," said Solway.
The national CTSA initiative grew out of a commitment by the NIH to re-engineer the clinical research enterprise, one of the key objectives of the NIH's "Roadmap." CTSA applicants were encouraged to create an academic home for clinical and translational science.
For this purpose, the University of Chicago created the Institute for Translational Medicine (ITM). Under Solway's direction, the ITM will operate across academic departments to generate new methods, tools and systems of discovery. The ITM will also interface closely with the committee on clinical and translational science, which will offer a novel curriculum in clinical and translational research.
The specific objectives of the ITM are to:
* Prepare physicians and scientists for careers in translational research.
* Create a seamless career path for young faculty seeking translational investigator status.
* Encourage high school, college, and allied health professions students to seek careers in translational research.
* Provide state-of-the-art resources for translational research, including access to expertise n clinical trial design, biostatistics, epidemiology, ethics, informatics, and regulatory issues.
* Provide comprehensive medical ethics training for current and future clinical and translational researchers.
* Provide a "home" for collaboration between departments and cooperating institutions.
* Enhance communication among investigators.
* Define the key genetic determinants of common, complex disorders.
* Utilize a "systems medicine" approach to treat common, complex disease.
The Medical Center is also preparing to launch a multi-faceted Urban Health Initiative (UHI), which will engage the community in developing clinical and community research agendas; involve community organizations in that research; accelerate the translation of health knowledge and expertise into and out of our community; and strive to reduce health disparities.
Source: John Easton
University of Chicago Medical Center
Yerkes Researchers Awarded $10 Million For Comparative Aging Study
Yerkes researchers will compare aging nonhuman primates to aging humans in an effort to develop more effective treatment options for aging-related diseases.
The National Institute of Aging has granted researchers at the Yerkes National Primate Research Center more than $10 million during a five-year period to compare changes that occur in normal aging humans, humans with Alzheimer's disease and humans with mild cognitive impairment to changes that occur in nonhuman primates, in particular chimpanzees and rhesus macaques. The goal of this study is to identify ways to diagnose aging-related diseases earlier in order to increase the chances for effective treatment as well as to develop new treatments based on specific physiological changes.
According to lead researcher Jim Herndon, PhD, "As humans age, verbal knowledge remains stable while short-term memory, working memory, mental processing speed and long-term memory decrease. Using Alzheimer's disease as the model, we are hopeful this study will help us determine how to detect the disease earlier in its course, thus increasing the chance for effective treatment. The study also may provide better understanding of specific physiological changes in humans that will be key in helping us develop the new treatments."
This aging study will be the first to use chimpanzees. According to Herndon, chimpanzees may provide the important evolutionary link to answer why humans are the longest living species and to determine if this characteristic is due to special cognitive capacities. This will be the first examination of chimp cognition in correlation with other aspects of aging.
The Yerkes Research Center is uniquely positioned to conduct this study. "With our well-established colony of chimpanzees and onsite, state-of-the-art imaging facility, Yerkes is one of but a few research centers that can undertake such an extensive aging-related study," said Stuart Zola, PhD, Yerkes director.
For more than seven decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to advancing scientific understanding of primate biology, behavior, veterinary care and conservation, and to improving human health and well-being. Today, the center, as one of only eight National Institutes of Health-funded national primate research centers, provides specialized scientific resources, expertise and training opportunities. Recognized as a multidisci¬plinary research institute, the Yerkes Research Center is making landmark discoveries in the fields of microbiol¬ogy and immunology, neuroscience, psychobiol¬ogy and sensory-motor systems. Research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer's disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progres¬sive illnesses such as Parkinson's and Alzheimer's; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.
Contact: Emily Rios
Emory University
The National Institute of Aging has granted researchers at the Yerkes National Primate Research Center more than $10 million during a five-year period to compare changes that occur in normal aging humans, humans with Alzheimer's disease and humans with mild cognitive impairment to changes that occur in nonhuman primates, in particular chimpanzees and rhesus macaques. The goal of this study is to identify ways to diagnose aging-related diseases earlier in order to increase the chances for effective treatment as well as to develop new treatments based on specific physiological changes.
According to lead researcher Jim Herndon, PhD, "As humans age, verbal knowledge remains stable while short-term memory, working memory, mental processing speed and long-term memory decrease. Using Alzheimer's disease as the model, we are hopeful this study will help us determine how to detect the disease earlier in its course, thus increasing the chance for effective treatment. The study also may provide better understanding of specific physiological changes in humans that will be key in helping us develop the new treatments."
This aging study will be the first to use chimpanzees. According to Herndon, chimpanzees may provide the important evolutionary link to answer why humans are the longest living species and to determine if this characteristic is due to special cognitive capacities. This will be the first examination of chimp cognition in correlation with other aspects of aging.
The Yerkes Research Center is uniquely positioned to conduct this study. "With our well-established colony of chimpanzees and onsite, state-of-the-art imaging facility, Yerkes is one of but a few research centers that can undertake such an extensive aging-related study," said Stuart Zola, PhD, Yerkes director.
For more than seven decades, the Yerkes National Primate Research Center, Emory University, has been dedicated to advancing scientific understanding of primate biology, behavior, veterinary care and conservation, and to improving human health and well-being. Today, the center, as one of only eight National Institutes of Health-funded national primate research centers, provides specialized scientific resources, expertise and training opportunities. Recognized as a multidisci¬plinary research institute, the Yerkes Research Center is making landmark discoveries in the fields of microbiol¬ogy and immunology, neuroscience, psychobiol¬ogy and sensory-motor systems. Research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases, such as AIDS and Alzheimer's disease; treat cocaine addiction; interpret brain activity through imaging; increase understanding of progres¬sive illnesses such as Parkinson's and Alzheimer's; unlock the secrets of memory; determine behavioral effects of hormone replacement therapy; address vision disorders; and advance knowledge about the evolutionary links between biology and behavior.
Contact: Emily Rios
Emory University
Living Taste Cells Produced Outside The Body
Researchers from the Monell Chemical Senses Center have succeeded in growing mature taste receptor cells outside the body and for the first time have been able to successfully keep the cells alive for a prolonged period of time. The establishment of a viable long-term model opens a range of new opportunities to increase scientists' understanding of the sense of taste and how it functions in nutrition, health and disease.
"We have an important new tool to help discover molecules that can enhance or block different kinds of tastes," explains principle investigator Nancy Rawson, PhD, a cellular biologist. "In addition, the success of this technique may provide hope for people who have lost their sense of taste due to radiation therapy or tissue damage, who typically lose weight and become malnourished. This system gives us a way to test for drugs that can promote recovery."
The findings are reported in an online issue of Chemical Senses.
Taste receptor cells are located in taste buds on the tongue and in the throat. These cells contain the receptors that detect taste stimuli: sweet, sour, salty, bitter, and umami (savory). Each taste receptor cell lives for only about 10-14 days, after which it is replaced. The new taste cells develop from a population of undifferentiated precursors known as basal cells.
Understanding of the process of taste cell differentiation, growth and turnover has been hampered by the inability of researchers to keep taste cells alive outside the body in controlled laboratory conditions.
To address this long-standing problem, the Monell researchers utilized a novel approach. Instead of starting with mature taste cells, they obtained basal cells from rat taste buds and placed these cells in a tissue culture system containing nutrients and growth factors. In this environment, the basal cells divided and differentiated into functional taste cells.
The new cells, which were kept alive for up to two months, were similar to mature taste cells in several key respects. A variety of methods were used to show that the cultured cells contain unique marker proteins characteristic of mature functioning taste receptor cells. In addition, functional assays revealed that the cultured cells responded to either bitter or sweet taste stimuli with increases of intracellular calcium, another property characteristic of mature taste cells.
Lead author Hakan Ozdener, MD, PhD, observes, "Although scientists have tried for many years to maintain taste cells in a long-term culture system, it was commonly believed that these cells could not be kept alive for longer than about 10 days. Now, we have demonstrated that taste cells can be generated in vitro and maintained for a prolonged period of time."
The taste cell culture system provides new insight into how basal cells turn into functional taste cells. Although previous dogma had held that induction was somehow dependent on interactions with the nervous system, the current findings suggest otherwise. Ozdener explains, "By producing new taste cells in an in vitro system, our results demonstrate that direct stimulation from nerves is not necessary to generate taste cells from precursors."
By using the cultured taste cells, researchers now have more precise control over the cell's surrounding environment, as well as better access to subcellular mechanisms, allowing them to ask certain questions that could not previously be addressed.
For instance, cultured cells can be used to study how taste stimuli interact to enhance good tastes or suppress unpleasant tastes. Similarly, new molecules, including potential artificial sweeteners or bitter blockers, can be evaluated to see if they interact with taste receptors to activate the cell.
Another important avenue for research aims to help people who have lost their sense of taste from radiation or diseases. Identification of factors that promote taste cell regeneration and growth may provide new avenues of treatment for these patients.
Researchers also hope to gain insight into how taste cell function changes across the lifespan, from infancy and childhood through old age.
Although the current experiments utilized rat taste cells, Ozdener, Rawson, and colleagues intend to use taste cell biopsies from humans to try to grow human taste cells.
Monell scientists Karen Yee, Jie Cao, Joseph Brand and John Teeter also contributed to the research, which was supported by grants from the National Science Foundation and from the Givaudan Flavors Corporation.
The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. For 35 years, Monell has been the nation's leading research center focused on understanding the senses of smell, taste and chemical irritation: how they function and affect lives from before birth through old age. Using a multidisciplinary approach, scientists collaborate in the areas of: sensation and perception, neuroscience and molecular biology, environmental and occupational health, nutrition and appetite, health and well being, and chemical ecology and communication. For more information about Monell, please visit monell/
Citation: Ozdener H, Yee KK, Cao J, Brand JG, Teeter JH, Rawson NE. Characterization and long-term maintenance of rat taste cells in culture. Chemical Senses advance online publication February 1, 2006; doi: 10.1093/chemse.bjj030.
Contact: Leslie Stein
steinmonell
Monell Chemical Senses Center
"We have an important new tool to help discover molecules that can enhance or block different kinds of tastes," explains principle investigator Nancy Rawson, PhD, a cellular biologist. "In addition, the success of this technique may provide hope for people who have lost their sense of taste due to radiation therapy or tissue damage, who typically lose weight and become malnourished. This system gives us a way to test for drugs that can promote recovery."
The findings are reported in an online issue of Chemical Senses.
Taste receptor cells are located in taste buds on the tongue and in the throat. These cells contain the receptors that detect taste stimuli: sweet, sour, salty, bitter, and umami (savory). Each taste receptor cell lives for only about 10-14 days, after which it is replaced. The new taste cells develop from a population of undifferentiated precursors known as basal cells.
Understanding of the process of taste cell differentiation, growth and turnover has been hampered by the inability of researchers to keep taste cells alive outside the body in controlled laboratory conditions.
To address this long-standing problem, the Monell researchers utilized a novel approach. Instead of starting with mature taste cells, they obtained basal cells from rat taste buds and placed these cells in a tissue culture system containing nutrients and growth factors. In this environment, the basal cells divided and differentiated into functional taste cells.
The new cells, which were kept alive for up to two months, were similar to mature taste cells in several key respects. A variety of methods were used to show that the cultured cells contain unique marker proteins characteristic of mature functioning taste receptor cells. In addition, functional assays revealed that the cultured cells responded to either bitter or sweet taste stimuli with increases of intracellular calcium, another property characteristic of mature taste cells.
Lead author Hakan Ozdener, MD, PhD, observes, "Although scientists have tried for many years to maintain taste cells in a long-term culture system, it was commonly believed that these cells could not be kept alive for longer than about 10 days. Now, we have demonstrated that taste cells can be generated in vitro and maintained for a prolonged period of time."
The taste cell culture system provides new insight into how basal cells turn into functional taste cells. Although previous dogma had held that induction was somehow dependent on interactions with the nervous system, the current findings suggest otherwise. Ozdener explains, "By producing new taste cells in an in vitro system, our results demonstrate that direct stimulation from nerves is not necessary to generate taste cells from precursors."
By using the cultured taste cells, researchers now have more precise control over the cell's surrounding environment, as well as better access to subcellular mechanisms, allowing them to ask certain questions that could not previously be addressed.
For instance, cultured cells can be used to study how taste stimuli interact to enhance good tastes or suppress unpleasant tastes. Similarly, new molecules, including potential artificial sweeteners or bitter blockers, can be evaluated to see if they interact with taste receptors to activate the cell.
Another important avenue for research aims to help people who have lost their sense of taste from radiation or diseases. Identification of factors that promote taste cell regeneration and growth may provide new avenues of treatment for these patients.
Researchers also hope to gain insight into how taste cell function changes across the lifespan, from infancy and childhood through old age.
Although the current experiments utilized rat taste cells, Ozdener, Rawson, and colleagues intend to use taste cell biopsies from humans to try to grow human taste cells.
Monell scientists Karen Yee, Jie Cao, Joseph Brand and John Teeter also contributed to the research, which was supported by grants from the National Science Foundation and from the Givaudan Flavors Corporation.
The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. For 35 years, Monell has been the nation's leading research center focused on understanding the senses of smell, taste and chemical irritation: how they function and affect lives from before birth through old age. Using a multidisciplinary approach, scientists collaborate in the areas of: sensation and perception, neuroscience and molecular biology, environmental and occupational health, nutrition and appetite, health and well being, and chemical ecology and communication. For more information about Monell, please visit monell/
Citation: Ozdener H, Yee KK, Cao J, Brand JG, Teeter JH, Rawson NE. Characterization and long-term maintenance of rat taste cells in culture. Chemical Senses advance online publication February 1, 2006; doi: 10.1093/chemse.bjj030.
Contact: Leslie Stein
steinmonell
Monell Chemical Senses Center
Animal Models That Help Translate Regenerative Therapies From Bench To Bedside
Clinical testing and development of novel therapies based on advances in tissue engineering and regenerative medicine that will one day enable the repair and replacement of diseased or damaged human muscle, bone, tendons, and ligaments depends on the availability of good animal models. The highlights of a recent workshop that explored the need for and current status of animal models for musculoskeletal regenerative medicine are presented in a special issue of Tissue Engineering, Part B: Reviews, a peer-reviewed journal published by Mary Ann Liebert, Inc. The issue is available free online (liebertpub/ten).
The production of specially engineered tissues to restore the function and viability of cartilage or meniscus in the knee, for example, or of degenerating intervertebral discs in the spine, will likely one day be commonplace. In the meantime, however, there is substantial need for better and standardized animal models for the development and testing of these innovative techniques. At the National Institutes of Health (NIH)-sponsored workshop "Translational Models for Musculoskeletal Tissue Engineering and Regenerative Medicine," leaders in the field described available models, outlined the unmet needs, and discussed the translational pathways for clinical testing and therapeutic use.
Mark Lee, PhD, and colleagues from the U.S. Food and Drug Administration (FDA, Rockville, MD) explained how the complexity of engineered tissue constructs, often containing a combination of cells, scaffolds, and other factors, creates challenges for product characterization and manufacturing. In their paper "Considerations for Tissue-Engineered and Regenerative Medicine Product Development Prior to Clinical Trials in the United States," they provide resources and recommendations to help product developers optimize the safety and effectiveness of engineered tissues ready for testing in clinical trials.
Focusing on the challenges of applying regenerative medicine technologies to the surgical repair of torn rotator cuffs, Kathleen Derwin, PhD, and coworkers from the Cleveland Clinic in Ohio identified appropriate animal models for research, development, and testing of repair strategies. In their paper, "Preclinical Models for Translating Regenerative Medicine Therapies for Rotator Cuff Repair," they emphasize the need for discriminating preclinical models in which researchers can experiment with the materials and procedures that will ultimately be used to treat human patients.
Damage and degeneration of cartilage is a leading cause of pain and disability associated with the development of osteoarthritis. In their review article "Animal Models for Cartilage Regeneration and Repair," Michal Szczodry, MD, Stephen Bruno, and Constance Chu, MD, from the University of Pittsburgh (Pennsylvania), emphasize the value of animal studies to understand the disease process underlying joint degeneration and to develop effective treatments for cartilage injuries.
"The workshop and manuscripts they produced provide an excellent summary of the tools we have available to translate new technologies forward, toward clinical studies. They also identify the critical gaps in our current knowledge," says Anthony Ratcliffe, PhD, President and CEO of Synthasome, Inc., and a guest editor of this special issue.
Source:
Vicki Cohn
Mary Ann Liebert, Inc./Genetic Engineering News
The production of specially engineered tissues to restore the function and viability of cartilage or meniscus in the knee, for example, or of degenerating intervertebral discs in the spine, will likely one day be commonplace. In the meantime, however, there is substantial need for better and standardized animal models for the development and testing of these innovative techniques. At the National Institutes of Health (NIH)-sponsored workshop "Translational Models for Musculoskeletal Tissue Engineering and Regenerative Medicine," leaders in the field described available models, outlined the unmet needs, and discussed the translational pathways for clinical testing and therapeutic use.
Mark Lee, PhD, and colleagues from the U.S. Food and Drug Administration (FDA, Rockville, MD) explained how the complexity of engineered tissue constructs, often containing a combination of cells, scaffolds, and other factors, creates challenges for product characterization and manufacturing. In their paper "Considerations for Tissue-Engineered and Regenerative Medicine Product Development Prior to Clinical Trials in the United States," they provide resources and recommendations to help product developers optimize the safety and effectiveness of engineered tissues ready for testing in clinical trials.
Focusing on the challenges of applying regenerative medicine technologies to the surgical repair of torn rotator cuffs, Kathleen Derwin, PhD, and coworkers from the Cleveland Clinic in Ohio identified appropriate animal models for research, development, and testing of repair strategies. In their paper, "Preclinical Models for Translating Regenerative Medicine Therapies for Rotator Cuff Repair," they emphasize the need for discriminating preclinical models in which researchers can experiment with the materials and procedures that will ultimately be used to treat human patients.
Damage and degeneration of cartilage is a leading cause of pain and disability associated with the development of osteoarthritis. In their review article "Animal Models for Cartilage Regeneration and Repair," Michal Szczodry, MD, Stephen Bruno, and Constance Chu, MD, from the University of Pittsburgh (Pennsylvania), emphasize the value of animal studies to understand the disease process underlying joint degeneration and to develop effective treatments for cartilage injuries.
"The workshop and manuscripts they produced provide an excellent summary of the tools we have available to translate new technologies forward, toward clinical studies. They also identify the critical gaps in our current knowledge," says Anthony Ratcliffe, PhD, President and CEO of Synthasome, Inc., and a guest editor of this special issue.
Source:
Vicki Cohn
Mary Ann Liebert, Inc./Genetic Engineering News
Potential Way To Reverse Cancer Cell Metabolism And Tumor Growth Identified By CSHL Study
A team of scientists led by Professor Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory has discovered molecular factors in cancer cells that boost the production of an enzyme that helps alter the cells' glucose metabolism. The altered metabolic state, called the Warburg effect, promotes extremely rapid cell proliferation and tumor growth.
Discovered eighty years ago by Nobel Prize-winning scientist Otto Warburg, this altered metabolism in cancer cells is most critically mediated by a protein called PK-M2 (pyruvate kinase M2). This is one of two versions - or isoforms - of the enzyme pyruvate kinase, whose other isoform, PK-M1, is harmless.
In a study published online ahead of print in the Proceedings of the National Academy of Sciences, Krainer and colleagues report their discovery of three factors that contribute to high levels of PK-M2 in cancer cells, in part by suppressing production of PK-M1.
"These findings suggest a new way in which cancer's altered glucose metabolism might be targeted for therapeutic benefit," explains Krainer. "Drugs that inhibit these factors and reverse the Warburg effect might work as anti-cancer agents." The study was performed in collaboration with Professor Lewis Cantley, Ph.D., and his colleagues at Harvard Medical School and The Broad Institute, in Cambridge, Mass.
Cancer cells consume glucose at a much higher rate than normal cells, but use very little glucose to produce energy, spending the rest instead on cell-building material. They also produce huge amounts of a byproduct called lactate. PK-M2, which facilitates this alternate metabolic lifestyle in cancer cells, was recently shown by the Cantley laboratory to be critical for tumor formation and growth.
This isoform and its non-cancerous counterpart PK-M1, which is found only in normal cells, both arise from the same gene, PK-M, via alternative splicing, a process that allows a single gene to produce multiple proteins. The initial RNA copy of a gene's DNA includes unnecessary pieces called introns that are first spliced out. The remaining bits, called exons, can be stitched back together in different ways by the cell's splicing machinery to form different RNAs that can then give rise to different proteins.
In the case of the PK-M gene, its RNA undergoes alternative splicing in a mutually exclusive fashion, giving rise to either the M1 or the M2 isoform. Krainer, an expert on alternative splicing, has been focused on understanding how the benign M1 isoform is switched off and the dangerous M2 isoform switched on in cancer cells. His team began by tracking down splicing factors and mechanisms that cause cancer cells to exclusively produce the M2 isoform.
By examining the levels of various splicing factors in numerous types of cancer cells, the scientists have narrowed the list of suspects to three proteins so far. All three are present at high levels in cancer cells, and repress the splicing of the harmless M1 isoform. This, by default, causes cells to produce only the M2 isoform.
The scientists could largely reverse this situation - restoring M1 production while decreasing M2 levels and lactate production - by forcing a reduction in the levels of the three splicing repressors. Whether this switch back to normal metabolism also impedes cancer cells' rapid growth remains to be tested.
"The cells didn't completely stop producing M2 when the three repressor proteins were blocked, which suggests that there might be other splicing factors that influence the switch between the two isoforms," explains Krainer. The team is now looking for these other potential splicing regulators.
"The field of cancer metabolism has reemerged, but several fundamental questions still remain about how the Warburg effect works," says Krainer. "We hope that our research on how alternative splicing regulates cellular metabolism will help fill in this puzzle and uncover new molecular drug targets."
The study was funded by a grant from the Starr Cancer Consortium.
"The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism" was published online before print on January 19, 2010, in PNAS. The full citation is: Cynthia V. Clower, Deblina Chatterjee, Zhenxun Wang, Lewis C. Cantley, Matthew G. Vander Heiden, and Adrian R. Krainer. The paper can be found at pnas/content/early/2010/01/11/0914845107.full.pdf+html
Source:
Peter Tarr
Cold Spring Harbor Laboratory
Discovered eighty years ago by Nobel Prize-winning scientist Otto Warburg, this altered metabolism in cancer cells is most critically mediated by a protein called PK-M2 (pyruvate kinase M2). This is one of two versions - or isoforms - of the enzyme pyruvate kinase, whose other isoform, PK-M1, is harmless.
In a study published online ahead of print in the Proceedings of the National Academy of Sciences, Krainer and colleagues report their discovery of three factors that contribute to high levels of PK-M2 in cancer cells, in part by suppressing production of PK-M1.
"These findings suggest a new way in which cancer's altered glucose metabolism might be targeted for therapeutic benefit," explains Krainer. "Drugs that inhibit these factors and reverse the Warburg effect might work as anti-cancer agents." The study was performed in collaboration with Professor Lewis Cantley, Ph.D., and his colleagues at Harvard Medical School and The Broad Institute, in Cambridge, Mass.
Cancer cells consume glucose at a much higher rate than normal cells, but use very little glucose to produce energy, spending the rest instead on cell-building material. They also produce huge amounts of a byproduct called lactate. PK-M2, which facilitates this alternate metabolic lifestyle in cancer cells, was recently shown by the Cantley laboratory to be critical for tumor formation and growth.
This isoform and its non-cancerous counterpart PK-M1, which is found only in normal cells, both arise from the same gene, PK-M, via alternative splicing, a process that allows a single gene to produce multiple proteins. The initial RNA copy of a gene's DNA includes unnecessary pieces called introns that are first spliced out. The remaining bits, called exons, can be stitched back together in different ways by the cell's splicing machinery to form different RNAs that can then give rise to different proteins.
In the case of the PK-M gene, its RNA undergoes alternative splicing in a mutually exclusive fashion, giving rise to either the M1 or the M2 isoform. Krainer, an expert on alternative splicing, has been focused on understanding how the benign M1 isoform is switched off and the dangerous M2 isoform switched on in cancer cells. His team began by tracking down splicing factors and mechanisms that cause cancer cells to exclusively produce the M2 isoform.
By examining the levels of various splicing factors in numerous types of cancer cells, the scientists have narrowed the list of suspects to three proteins so far. All three are present at high levels in cancer cells, and repress the splicing of the harmless M1 isoform. This, by default, causes cells to produce only the M2 isoform.
The scientists could largely reverse this situation - restoring M1 production while decreasing M2 levels and lactate production - by forcing a reduction in the levels of the three splicing repressors. Whether this switch back to normal metabolism also impedes cancer cells' rapid growth remains to be tested.
"The cells didn't completely stop producing M2 when the three repressor proteins were blocked, which suggests that there might be other splicing factors that influence the switch between the two isoforms," explains Krainer. The team is now looking for these other potential splicing regulators.
"The field of cancer metabolism has reemerged, but several fundamental questions still remain about how the Warburg effect works," says Krainer. "We hope that our research on how alternative splicing regulates cellular metabolism will help fill in this puzzle and uncover new molecular drug targets."
The study was funded by a grant from the Starr Cancer Consortium.
"The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism" was published online before print on January 19, 2010, in PNAS. The full citation is: Cynthia V. Clower, Deblina Chatterjee, Zhenxun Wang, Lewis C. Cantley, Matthew G. Vander Heiden, and Adrian R. Krainer. The paper can be found at pnas/content/early/2010/01/11/0914845107.full.pdf+html
Source:
Peter Tarr
Cold Spring Harbor Laboratory
Shrink Nanotechnologies Unveils Product Image Of Initial StemDisc450 Prototype
Shrink Nanotechnologies, Inc. ("Shrink") (OTC Bulletin Board: INKN), an innovative nanotechnology company developing products and licensing opportunities in the alternative energy industry, medical diagnostics and sensors and biotechnology research and development tools businesses, revealed an image of its first product offering the StemDisc450™, a high-yield, low cost, patent-pending cell culturing biomedical research tool. Shrink expects to begin offering this product for sale in the latter part of 2010.
"Tissue engineering and cell culturing are high growth areas of the biotechnology field. This trend is being fueled as the idea of 'personalized medicine' or 'therapeutics and treatments made for you' becomes a reality. And as the personalized medicine movement grows, biotech and pharmaceutical companies are focusing on the promise of novel research, especially new cellular-based therapies, to help combat cancer, spinal cord injuries, diabetes, Parkinson's and Alzheimer's disease, and many more. StemDisc is a platform for Shrink to offer a growing suite of products that will address an important spectrum of the needs within cellular and tissue engineering technologies and tools," Mark L. Baum, CEO of Shrink Nanotechnologies, Inc.
"We have started field testing of our first StemDisc450 prototypes, and we anticipate being able to show time lapse videos of this product performing, and actually developing HESCs (human embryonic stem cells) and IPSCs (induced pluripotent stem cells)," added Baum. "Shrink is exploring opportunities with established stem cell R&D companies for potential strategic partnerships for the sale and marketing of StemDisc™ products. Our primary target market is the more than 3,000 stem cell research labs and 15,000 biomedical laboratories operating in the United States."
About StemDisc
StemDisc is designed to improve embryoid body (EB) formation of stem cells at a higher rate and efficiency over current EB formation methods. The platform can be used to grow and differentiate human and animal single cells, human embryonic stem cells (HESCs) and induced pluri-potent stem cells (IPSCs). Versions of StemDisc's unique honeycomb-like well will be offered in different diameter and depth depending on the type of cell and application. Each round bottom "microwell" is capable of making 800 to 1,000 EBs, increasing the flexibility of use for researchers to achieve optimum EB formation with high reliability compared to legacy methods. A unique feature of the StemDisc product line is the optical transparency of the surface that the cells rest in. The StemDisc polymer offers amazing transparency, providing the cell biologist with the ability to see more of what she is doing as she completes her research. StemDisc's five micron walls between microwells virtually assure a clean transfer of the biological material into a well in a few easy steps, helping to further lower costs and accelerate the time to publish results of potentially life-saving studies.
Statements contained herein that are not historical facts may be forward-looking statements within the meaning of the Securities Act of 1933, as amended. Forward-looking statements include statements regarding the intent, belief or current expectations of the Company and its management. Such statements are estimates only. Actual results may differ materially from those anticipated in this press release. Such statements reflect management's current views, are based on certain assumptions and involve risks and uncertainties. Actual results, events, or performance may differ materially from the above forward-looking statements due to a number of important factors, and will be dependent upon a variety of factors, including, but not limited to Shrink's ability to obtain additional financing and to build and develop markets for Shrink's biotechnology technologies and products. These factors should be strongly considered when making a decision to acquire or maintain a financial interest in Shrink, including consulting with a FINRA registered representative prior to making such decision. Shrink undertakes no obligation to publicly update these forward-looking statements to reflect events or circumstances that occur after the date hereof or to reflect any change in Shrink's expectations with regard to these forward-looking statements or the occurrence of unanticipated events. Factors that may impact Shrink's success are more fully disclosed in Shrink's most recent public filings with the U.S. Securities and Exchange Commission.
Source: Shrink Nanotechnologies, Inc
"Tissue engineering and cell culturing are high growth areas of the biotechnology field. This trend is being fueled as the idea of 'personalized medicine' or 'therapeutics and treatments made for you' becomes a reality. And as the personalized medicine movement grows, biotech and pharmaceutical companies are focusing on the promise of novel research, especially new cellular-based therapies, to help combat cancer, spinal cord injuries, diabetes, Parkinson's and Alzheimer's disease, and many more. StemDisc is a platform for Shrink to offer a growing suite of products that will address an important spectrum of the needs within cellular and tissue engineering technologies and tools," Mark L. Baum, CEO of Shrink Nanotechnologies, Inc.
"We have started field testing of our first StemDisc450 prototypes, and we anticipate being able to show time lapse videos of this product performing, and actually developing HESCs (human embryonic stem cells) and IPSCs (induced pluripotent stem cells)," added Baum. "Shrink is exploring opportunities with established stem cell R&D companies for potential strategic partnerships for the sale and marketing of StemDisc™ products. Our primary target market is the more than 3,000 stem cell research labs and 15,000 biomedical laboratories operating in the United States."
About StemDisc
StemDisc is designed to improve embryoid body (EB) formation of stem cells at a higher rate and efficiency over current EB formation methods. The platform can be used to grow and differentiate human and animal single cells, human embryonic stem cells (HESCs) and induced pluri-potent stem cells (IPSCs). Versions of StemDisc's unique honeycomb-like well will be offered in different diameter and depth depending on the type of cell and application. Each round bottom "microwell" is capable of making 800 to 1,000 EBs, increasing the flexibility of use for researchers to achieve optimum EB formation with high reliability compared to legacy methods. A unique feature of the StemDisc product line is the optical transparency of the surface that the cells rest in. The StemDisc polymer offers amazing transparency, providing the cell biologist with the ability to see more of what she is doing as she completes her research. StemDisc's five micron walls between microwells virtually assure a clean transfer of the biological material into a well in a few easy steps, helping to further lower costs and accelerate the time to publish results of potentially life-saving studies.
Statements contained herein that are not historical facts may be forward-looking statements within the meaning of the Securities Act of 1933, as amended. Forward-looking statements include statements regarding the intent, belief or current expectations of the Company and its management. Such statements are estimates only. Actual results may differ materially from those anticipated in this press release. Such statements reflect management's current views, are based on certain assumptions and involve risks and uncertainties. Actual results, events, or performance may differ materially from the above forward-looking statements due to a number of important factors, and will be dependent upon a variety of factors, including, but not limited to Shrink's ability to obtain additional financing and to build and develop markets for Shrink's biotechnology technologies and products. These factors should be strongly considered when making a decision to acquire or maintain a financial interest in Shrink, including consulting with a FINRA registered representative prior to making such decision. Shrink undertakes no obligation to publicly update these forward-looking statements to reflect events or circumstances that occur after the date hereof or to reflect any change in Shrink's expectations with regard to these forward-looking statements or the occurrence of unanticipated events. Factors that may impact Shrink's success are more fully disclosed in Shrink's most recent public filings with the U.S. Securities and Exchange Commission.
Source: Shrink Nanotechnologies, Inc
Gene That 'Cancer-Proofs' Rodent's Cells Discovered By Scientists
Despite a 30-year lifespan that gives ample time for cells to grow cancerous, a small rodent species called a naked mole rat has never been found with tumors of any kind - and now biologists at the University of Rochester think they know why.
The findings, presented in The Proceedings of the National Academy of Sciences, show that the mole rat's cells express a gene called p16 that makes the cells "claustrophobic," stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells' growth barely changed, whereas regular mouse cells became fully cancerous.
"We think we've found the reason these mole rats don't get cancer, and it's a bit of a surprise," says Vera Gorbunova, associate professor of biology at the University of Rochester and lead investigator on the discovery. "It's very early to speculate about the implications, but if the effect of p16 can be simulated in humans we might have a way to halt cancer before it starts."
Naked mole rats are strange, ugly, nearly hairless mouse-like creatures that live in underground communities. Unlike any other mammal, these communities consist of queens and workers more reminiscent of bees than rodents. Naked mole rats can live up to 30 years, which is exceptionally long for a small rodent. Despite large numbers of naked mole-rats under observation, there has never been a single recorded case of a mole rat contracting cancer, says Gorbunova. Adding to their mystery is the fact that mole rats appear to age very little until the very end of their lives.
Over the last three years, Gorbunova and Andrei Seluanov, research professor of biology at the University of Rochester, have worked an unusual angle on the quest to understand cancer: Investigating rodents from across the globe to get an idea of the similarities and differences of how varied but closely related species deal with cancer.
In 2006, Gorbunova discovered that telomerase - an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer - is highly active in small rodents, but not in large ones.
Until Gorbunova and Seluanov's research, the prevailing wisdom had assumed that an animal that lived as long as we humans do needed to suppress telomerase activity to guard against cancer. Telomerase helps cells reproduce, and cancer is essentially runaway cellular reproduction, so an animal living for 70 years has a lot of chances for its cells to mutate into cancer, says Gorbunova. A mouse's life expectancy is shortened by other factors in nature, such as predation, so it was thought the mouse could afford the slim cancer risk to benefit from telomerase's ability to speed healing.
While the findings were a surprise, they revealed another question: What about small animals like the common grey squirrel that live for 24 years or more? With telomerase fully active over such a long period, why isn't cancer rampant in these creatures?
Gorbunova sought to answer that question, and in 2008 confirmed that small-bodied rodents with long lifespans had evolved a previously unknown anti-cancer mechanism that appears to be different from any anticancer mechanisms employed by humans or other large mammals.
At the time she was not able to identify just what the mechanism might be, saying: "We haven't come across this anticancer mechanism before because it doesn't exist in the two species most often used for cancer research: mice and humans. Mice are short-lived and humans are large-bodied. But this mechanism appears to exist only in small, long-lived animals."
Now, Gorbunova believes she has found the primary reason these small animals are staying cancer-free, and it appears to be a kind of overcrowding early-warning gene that the naked mole rat expresses in its cells.
When Gorbunova and her team began specifically investigating mole rat cells, they were surprised at how difficult it was to grow the cells in the lab for study. The cells simply refused to replicate once a certain number of them occupied a space. Other cells, such as human cells, also cease replication when their populations become too dense, but the mole rat cells were reaching their limit much earlier than other animals' cells.
"Since cancer is basically runaway cell replication, we realized that whatever was doing this was probably the same thing that prevented cancer from ever getting started in the mole rats," says Gorbunova.
Like many animals, including humans, the mole rats have a gene called p27 that prevents cellular overcrowding, but the mole rats use another, earlier defense in gene p16. Cancer cells tend to find ways around p27, but mole rats have a double barrier that a cell must overcome before it can grow uncontrollably.
"We believe the additional layer of protection conferred by this two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole rat," says Gorbunova in the PNAS paper.
Gorbunova and Seluanov are now planning to delve deeper into the mole rat's genetics to see if their cancer resistance might be applicable to humans.
This research was funded by the National Institutes of Health and the Ellison Medical Foundation.
Source:
Jonathan Sherwood
University of Rochester
The findings, presented in The Proceedings of the National Academy of Sciences, show that the mole rat's cells express a gene called p16 that makes the cells "claustrophobic," stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells' growth barely changed, whereas regular mouse cells became fully cancerous.
"We think we've found the reason these mole rats don't get cancer, and it's a bit of a surprise," says Vera Gorbunova, associate professor of biology at the University of Rochester and lead investigator on the discovery. "It's very early to speculate about the implications, but if the effect of p16 can be simulated in humans we might have a way to halt cancer before it starts."
Naked mole rats are strange, ugly, nearly hairless mouse-like creatures that live in underground communities. Unlike any other mammal, these communities consist of queens and workers more reminiscent of bees than rodents. Naked mole rats can live up to 30 years, which is exceptionally long for a small rodent. Despite large numbers of naked mole-rats under observation, there has never been a single recorded case of a mole rat contracting cancer, says Gorbunova. Adding to their mystery is the fact that mole rats appear to age very little until the very end of their lives.
Over the last three years, Gorbunova and Andrei Seluanov, research professor of biology at the University of Rochester, have worked an unusual angle on the quest to understand cancer: Investigating rodents from across the globe to get an idea of the similarities and differences of how varied but closely related species deal with cancer.
In 2006, Gorbunova discovered that telomerase - an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer - is highly active in small rodents, but not in large ones.
Until Gorbunova and Seluanov's research, the prevailing wisdom had assumed that an animal that lived as long as we humans do needed to suppress telomerase activity to guard against cancer. Telomerase helps cells reproduce, and cancer is essentially runaway cellular reproduction, so an animal living for 70 years has a lot of chances for its cells to mutate into cancer, says Gorbunova. A mouse's life expectancy is shortened by other factors in nature, such as predation, so it was thought the mouse could afford the slim cancer risk to benefit from telomerase's ability to speed healing.
While the findings were a surprise, they revealed another question: What about small animals like the common grey squirrel that live for 24 years or more? With telomerase fully active over such a long period, why isn't cancer rampant in these creatures?
Gorbunova sought to answer that question, and in 2008 confirmed that small-bodied rodents with long lifespans had evolved a previously unknown anti-cancer mechanism that appears to be different from any anticancer mechanisms employed by humans or other large mammals.
At the time she was not able to identify just what the mechanism might be, saying: "We haven't come across this anticancer mechanism before because it doesn't exist in the two species most often used for cancer research: mice and humans. Mice are short-lived and humans are large-bodied. But this mechanism appears to exist only in small, long-lived animals."
Now, Gorbunova believes she has found the primary reason these small animals are staying cancer-free, and it appears to be a kind of overcrowding early-warning gene that the naked mole rat expresses in its cells.
When Gorbunova and her team began specifically investigating mole rat cells, they were surprised at how difficult it was to grow the cells in the lab for study. The cells simply refused to replicate once a certain number of them occupied a space. Other cells, such as human cells, also cease replication when their populations become too dense, but the mole rat cells were reaching their limit much earlier than other animals' cells.
"Since cancer is basically runaway cell replication, we realized that whatever was doing this was probably the same thing that prevented cancer from ever getting started in the mole rats," says Gorbunova.
Like many animals, including humans, the mole rats have a gene called p27 that prevents cellular overcrowding, but the mole rats use another, earlier defense in gene p16. Cancer cells tend to find ways around p27, but mole rats have a double barrier that a cell must overcome before it can grow uncontrollably.
"We believe the additional layer of protection conferred by this two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole rat," says Gorbunova in the PNAS paper.
Gorbunova and Seluanov are now planning to delve deeper into the mole rat's genetics to see if their cancer resistance might be applicable to humans.
This research was funded by the National Institutes of Health and the Ellison Medical Foundation.
Source:
Jonathan Sherwood
University of Rochester
Targeted Removal Of Genes Can Restore Cellular Function In Cells With Genetic Defects
Gene therapy, in which a working gene is inserted into a cell to replace a faulty or absent gene, is a promising experimental technique for the prevention and treatment of disease.
Now a research team led by a Northwestern University physicist reports that a counterintuitive approach also holds promise. The targeted removal of genes -- the exact opposite of what a gene therapist would do -- can restore cellular function in cells with genetic defects, such as mutations.
Published online in the journal Molecular Systems Biology, the results have ramifications for medical research as well as for optimizing certain metabolic processes used in the production of biofuels, such as ethanol.
After gathering extensive experimental information on the metabolic networks of three different single-celled organisms, the researchers built a general quantitative model that can be used to control and restore biological function to cells impaired by a genetic defect or by other factors that compromise gene activity. Their network-based method does this by targeted deletion of genes, forcing the cell to either bypass the functions affected by the defective gene or to compensate for the lost function.
The research, led by Adilson E. Motter, assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and the paper's lead author, grew out of Motter's earlier work on the U.S. power grid -- another complex system that is very different from biological systems but also with many similarities.
After the 2003 Northeast blackout, where a sequence of failures in the power grid led to the largest outage in U.S. history, experts determined that the event could have been reduced or avoided by instigating small intentional blackouts in the system during the initial hours of instability.
"And the same could be valid in biology, where a defective gene may trigger a cascade of 'failures' along the cellular network," said Motter, whose interest and expertise lie in complex systems and understanding how the structure and dynamics of a high-dimensional system, such as an intracellular network or a power grid, relate to its function.
"Our recent research shows that what is true in power networks is also true in biological networks. Inflicting a small amount of damage can control what otherwise would be much more significant damage."
With the experimental information assembled, the researchers used their computer model to simulate the organism and its function. They started with a perfect cell and then, with a key gene deletion, damaged the cell so that it was unable to grow or had a significantly reduced growth rate.
Next, the researchers restored growth by deleting additional genes, which stimulated the cell to make a different choice and use different pathways. Interestingly, the cell's recovery was stronger when more genes were deleted. They could even restore growth to non-growing mutant cells; the researchers dubbed this the "Lazarus effect."
"Our research is based on optimizing the use of resources already available in the cell," said Motter. "We are exploring existing reactions and genes in the cell that the cell would not use or use to a lesser degree under normal conditions. This is different from traditional gene therapy, which is based on introducing new genes into the cell -- with its own advantages and problems because of that."
The team's use of predictive models is similar to how physicists use models, for example, to determine the position of the moon tomorrow at a specific time. Thanks to the recent wealth of available biological information, computational scientists now are beginning to develop quantitative models of biological systems that allow them to predict cellular behavior.
In one in silico experiment (via computer simulation) with E. coli, the researchers found that the deletion of one gene is lethal to the cell but when that same gene is removed along with other genes, it is not lethal. The gene, it turns out, is only essential in the presence of other genes. This touches the issue, says Motter, of whether organisms have an unconditional set of essential genes.
While Motter's team has not done actual laboratory experiments, they have used their computational results to re-interpret and explain specific recent experimental results. They have applied physics methods to solve a biological problem. Their method, for example, can identify the genes whose removal restores growth in gene-deficient mutants of E. coli and S. cerevisiae, a type of yeast.
"From a phylogenetic viewpoint, yeast is more similar to humans than E. coli," said Motter, a member of the Northwestern Institute on Complex Systems. "Of course, there is a distance between single-celled organisms and human cells, but our results should be seen as proof of principle. Many experimentalists are interested in our work, and part of this interest comes from its potential for disease treatment research. This work is a concrete application of complex networks to solve a real problem, and, as such, also requires substantial involvement of network theorists."
"Needless to say, this work is built on previous research and would not have been possible without the very significant contribution of my collaborators," said Motter.
In addition to Motter, other authors of the paper, titled "Predicting synthetic rescues in metabolic networks," are Natali Gulbahce, of Los Alamos National Laboratory and Dana Farber Cancer Institute; Eivind Almaas, of Lawrence Livermore National Laboratory; and Albert-LГЎszlГі BarabГЎsi, of Northeastern University.
The Molecular Systems Biology paper can be viewed at nature/msb/journal/v4/n1/full/msb20081.html.
Source: Megan Fellman
Northwestern University
Now a research team led by a Northwestern University physicist reports that a counterintuitive approach also holds promise. The targeted removal of genes -- the exact opposite of what a gene therapist would do -- can restore cellular function in cells with genetic defects, such as mutations.
Published online in the journal Molecular Systems Biology, the results have ramifications for medical research as well as for optimizing certain metabolic processes used in the production of biofuels, such as ethanol.
After gathering extensive experimental information on the metabolic networks of three different single-celled organisms, the researchers built a general quantitative model that can be used to control and restore biological function to cells impaired by a genetic defect or by other factors that compromise gene activity. Their network-based method does this by targeted deletion of genes, forcing the cell to either bypass the functions affected by the defective gene or to compensate for the lost function.
The research, led by Adilson E. Motter, assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and the paper's lead author, grew out of Motter's earlier work on the U.S. power grid -- another complex system that is very different from biological systems but also with many similarities.
After the 2003 Northeast blackout, where a sequence of failures in the power grid led to the largest outage in U.S. history, experts determined that the event could have been reduced or avoided by instigating small intentional blackouts in the system during the initial hours of instability.
"And the same could be valid in biology, where a defective gene may trigger a cascade of 'failures' along the cellular network," said Motter, whose interest and expertise lie in complex systems and understanding how the structure and dynamics of a high-dimensional system, such as an intracellular network or a power grid, relate to its function.
"Our recent research shows that what is true in power networks is also true in biological networks. Inflicting a small amount of damage can control what otherwise would be much more significant damage."
With the experimental information assembled, the researchers used their computer model to simulate the organism and its function. They started with a perfect cell and then, with a key gene deletion, damaged the cell so that it was unable to grow or had a significantly reduced growth rate.
Next, the researchers restored growth by deleting additional genes, which stimulated the cell to make a different choice and use different pathways. Interestingly, the cell's recovery was stronger when more genes were deleted. They could even restore growth to non-growing mutant cells; the researchers dubbed this the "Lazarus effect."
"Our research is based on optimizing the use of resources already available in the cell," said Motter. "We are exploring existing reactions and genes in the cell that the cell would not use or use to a lesser degree under normal conditions. This is different from traditional gene therapy, which is based on introducing new genes into the cell -- with its own advantages and problems because of that."
The team's use of predictive models is similar to how physicists use models, for example, to determine the position of the moon tomorrow at a specific time. Thanks to the recent wealth of available biological information, computational scientists now are beginning to develop quantitative models of biological systems that allow them to predict cellular behavior.
In one in silico experiment (via computer simulation) with E. coli, the researchers found that the deletion of one gene is lethal to the cell but when that same gene is removed along with other genes, it is not lethal. The gene, it turns out, is only essential in the presence of other genes. This touches the issue, says Motter, of whether organisms have an unconditional set of essential genes.
While Motter's team has not done actual laboratory experiments, they have used their computational results to re-interpret and explain specific recent experimental results. They have applied physics methods to solve a biological problem. Their method, for example, can identify the genes whose removal restores growth in gene-deficient mutants of E. coli and S. cerevisiae, a type of yeast.
"From a phylogenetic viewpoint, yeast is more similar to humans than E. coli," said Motter, a member of the Northwestern Institute on Complex Systems. "Of course, there is a distance between single-celled organisms and human cells, but our results should be seen as proof of principle. Many experimentalists are interested in our work, and part of this interest comes from its potential for disease treatment research. This work is a concrete application of complex networks to solve a real problem, and, as such, also requires substantial involvement of network theorists."
"Needless to say, this work is built on previous research and would not have been possible without the very significant contribution of my collaborators," said Motter.
In addition to Motter, other authors of the paper, titled "Predicting synthetic rescues in metabolic networks," are Natali Gulbahce, of Los Alamos National Laboratory and Dana Farber Cancer Institute; Eivind Almaas, of Lawrence Livermore National Laboratory; and Albert-LГЎszlГі BarabГЎsi, of Northeastern University.
The Molecular Systems Biology paper can be viewed at nature/msb/journal/v4/n1/full/msb20081.html.
Source: Megan Fellman
Northwestern University
Cardiovascular Disease Targeted By New Nanoparticles
Researchers at MIT and Harvard Medical School have built targeted nanoparticles that can cling to artery walls and slowly release medicine, an advance that potentially provides an alternative to drug-releasing stents in some patients with cardiovascular disease.
The particles, dubbed "nanoburrs" because they are coated with tiny protein fragments that allow them to stick to target proteins, can be designed to release their drug payload over several days. They are one of the first such particles that can precisely home in on damaged vascular tissue, says Omid Farokhzad, associate professor at Harvard Medical School and an author of a paper describing the nanoparticles in the Jan. 18 issue of the Proceedings of the National Academy of Sciences.
Farokhzad and MIT Institute Professor Robert Langer, also an author of the paper, have previously developed nanoparticles that seek out and destroy tumors.
The nanoburrs are targeted to a specific structure, known as the basement membrane, which lines the arterial walls and is only exposed when those walls are damaged. Therefore, the nanoburrs could be used to deliver drugs to treat atherosclerosis and other inflammatory cardiovascular diseases. In the current study, the team used paclitaxel, a drug that inhibits cell division and helps prevent the growth of scar tissue that can clog arteries.
"This is a very exciting example of nanotechnology and cell targeting in action that I hope will have broad ramifications," says Langer.
The researchers hope the particles could become a complementary approach that can be used with vascular stents, which are the standard of care for most cases of clogged and damaged arteries, or in lieu of stents in areas not well suited to them, such as near a fork in the artery.
The particles, which are spheres 60 nanometers in diameter, consist of three layers: an inner core containing a complex of the drug and a polymer chain called PLA; a middle layer of soybean lecithin, a fatty material; and an outer coating of a polymer called PEG, which protects the particle as it travels through the bloodstream.
The drug can only be released when it detaches from the PLA polymer chain, which occurs gradually by a reaction called ester hydrolysis. The longer the polymer chain, the longer this process takes, so the researchers can control the timing of the drug's release by altering the chain length. So far, they have achieved drug release over 12 days, in tests in cultured cells.
In tests in rats, the researchers showed that the nanoburrs can be injected intravenously into the tail and still reach their intended target - damaged walls of the left carotid artery. The burrs bound to the damaged walls at twice the rate of nontargeted nanoparticles.
Because the particles can deliver drugs over a longer period of time, and can be injected intravenously, patients would not have to endure repeated and surgically invasive injections directly into the area that requires treatment, says Juliana Chan, a graduate student in Langer's lab and lead author of the paper.
How they did it: The researchers screened a library of short peptide sequences to find one that binds most effectively to molecules on the surface of the basement membrane. They used the most effective one, a seven-amino-acid sequence dubbed C11, to coat the outer layer of their nanoparticles.
Next steps: The team is testing the nanoburrs in rats over a two-week period to determine the most effective dose for treating damaged vascular tissue. The particles may also prove useful in delivering drugs to tumors.
"This technology could have broad applications across other important diseases, including cancer and inflammatory diseases where vascular permeability or vascular damage is commonly observed," says Farokhzad.
"Spatiotemporal controlled delivery of nanoparticles to injured vasculature," Juliana Chan, Liangfang Zhang, Rong Tong, Debuyati Ghosh, Weiwei Gao, Grace Liao, Kai Yuet, David Gray, June-Wha Rhee, Jianjun Cheng, Gershon Golomb, Peter Libby, Robert Langer, Omid Farokhzad. Proceedings of the National Academy of Sciences, week of Jan. 18, 2010.
Source: Jen Hirsch
Massachusetts Institute of Technology
The particles, dubbed "nanoburrs" because they are coated with tiny protein fragments that allow them to stick to target proteins, can be designed to release their drug payload over several days. They are one of the first such particles that can precisely home in on damaged vascular tissue, says Omid Farokhzad, associate professor at Harvard Medical School and an author of a paper describing the nanoparticles in the Jan. 18 issue of the Proceedings of the National Academy of Sciences.
Farokhzad and MIT Institute Professor Robert Langer, also an author of the paper, have previously developed nanoparticles that seek out and destroy tumors.
The nanoburrs are targeted to a specific structure, known as the basement membrane, which lines the arterial walls and is only exposed when those walls are damaged. Therefore, the nanoburrs could be used to deliver drugs to treat atherosclerosis and other inflammatory cardiovascular diseases. In the current study, the team used paclitaxel, a drug that inhibits cell division and helps prevent the growth of scar tissue that can clog arteries.
"This is a very exciting example of nanotechnology and cell targeting in action that I hope will have broad ramifications," says Langer.
The researchers hope the particles could become a complementary approach that can be used with vascular stents, which are the standard of care for most cases of clogged and damaged arteries, or in lieu of stents in areas not well suited to them, such as near a fork in the artery.
The particles, which are spheres 60 nanometers in diameter, consist of three layers: an inner core containing a complex of the drug and a polymer chain called PLA; a middle layer of soybean lecithin, a fatty material; and an outer coating of a polymer called PEG, which protects the particle as it travels through the bloodstream.
The drug can only be released when it detaches from the PLA polymer chain, which occurs gradually by a reaction called ester hydrolysis. The longer the polymer chain, the longer this process takes, so the researchers can control the timing of the drug's release by altering the chain length. So far, they have achieved drug release over 12 days, in tests in cultured cells.
In tests in rats, the researchers showed that the nanoburrs can be injected intravenously into the tail and still reach their intended target - damaged walls of the left carotid artery. The burrs bound to the damaged walls at twice the rate of nontargeted nanoparticles.
Because the particles can deliver drugs over a longer period of time, and can be injected intravenously, patients would not have to endure repeated and surgically invasive injections directly into the area that requires treatment, says Juliana Chan, a graduate student in Langer's lab and lead author of the paper.
How they did it: The researchers screened a library of short peptide sequences to find one that binds most effectively to molecules on the surface of the basement membrane. They used the most effective one, a seven-amino-acid sequence dubbed C11, to coat the outer layer of their nanoparticles.
Next steps: The team is testing the nanoburrs in rats over a two-week period to determine the most effective dose for treating damaged vascular tissue. The particles may also prove useful in delivering drugs to tumors.
"This technology could have broad applications across other important diseases, including cancer and inflammatory diseases where vascular permeability or vascular damage is commonly observed," says Farokhzad.
"Spatiotemporal controlled delivery of nanoparticles to injured vasculature," Juliana Chan, Liangfang Zhang, Rong Tong, Debuyati Ghosh, Weiwei Gao, Grace Liao, Kai Yuet, David Gray, June-Wha Rhee, Jianjun Cheng, Gershon Golomb, Peter Libby, Robert Langer, Omid Farokhzad. Proceedings of the National Academy of Sciences, week of Jan. 18, 2010.
Source: Jen Hirsch
Massachusetts Institute of Technology
Protein Structure Solved, Revealing Secrets Of Cell Membranes
A team of scientists at The Scripps Research Institute and the National Institutes of Health (NIH) has discovered the structure of a protein that pinches off tiny pouches from cells' outer membranes. Cells use these pouches, or vesicles, to carry nutrients and other essential substances, but many medicines also hitch a ride inside them.
The structure of the protein, called dynamin, is helping to answer many longstanding questions about how vesicles form, advancing knowledge of a process critical to cell survival. The findings may also have implications for designing better ways for delivering drugs.
The research was published on April 28, 2010, in an advance, online issue of the prestigious journal Nature.
The Puzzle of Pinching Off Membranes
The cell membrane typically acts as a barrier around the cell, keeping out harmful materials. But cells also need some substances to get inside.
To get past the membrane, nutrients or hormones in the bloodstream, for example, bind to specific receptors on cells membranes. The membrane then forms a pit around these bound molecules, which is squeezed into a pouch, or vesicle, that detaches from the rest of the cell membrane and carries its essential cargo into the cell. Nerve cells use this same vesicle-making mechanism, called endocytosis, to maintain signaling from one cell to another.
"Endocytosis is how cells communicate," says Sandra Schmid, chair of the Scripps Department of Cell Biology and senior author of the Nature article along with Fred Dyda at NIH. "It's critical for many biological functions from controlling blood pressure to getting rid of glucose."
Despite the importance of endocytosis, scientists have been puzzled by how cells perform this process. But they knew that at least one molecule, dynamin, played a starring role.
Dynamin belongs to a large family of enzymes called GTPases. These enzymes bind a chemical called GTP and convert it to a simpler form (GDP), releasing energy in the process. During this conversion a GTPase undergoes a change in shape, enabling it to perform a particular function - such as making vesicles.
Initially, most scientists believed that many dynamin molecules assembled long spirals on cell membranes, and that in the presence of GTP these spirals tightened, lopping off a vesicle.
But a year ago, a study published in Cell by Schmid's group challenged that view. By watching vesicle transformation through a microscope, the scientists showed that dynamin proteins only form a short collar around the cell membrane. What's more, dynamin can act alone, without the help of any other proteins.
"Dynamin is the master regulator of endocytosis," says Schmid. "It is involved at every stage of vesicle formation."
Seeing Is Believing
That study did not reveal how the dynamin collars pinch off membrane vesicles, though. Thus, Schmid and others turned their attention to dynamin's GTPase activity for clues of how it controls the process.
One way to figure out how a protein functions is to determine its structure. To this end, scientists often use a technique called X-ray crystallography, which involves making crystals of the protein of interest and then bombarding them with X-rays to see the positions of the atoms.
But dynamin is a large molecule, containing almost 1,000 amino acids, making it difficult to crystallize. To overcome the problem, about three years ago Joshua Chappie, then a graduate student in Schmid's laboratory, engineered a shorter version of dynamin that retained the same GTPase activity as the complete protein.
With this shortened protein Chappi quickly obtained crystals and then examined them by X-ray crystallography. However, the resulting data proved impossible to interpret because of a kind of double vision in the X-ray signals. Then came a breakthrough: Chappie discovered that the minimal dynamin formed dimers during its normal cycle of GTP hydrolysis.
Researchers knew that dynamin is found in cells as a group of four molecules, or a tetramer. Like a handful of Tootsie Pops™, dynamin tetramers are held together by long stalk regions with the GTPase domains protruding from their tops. However, the minimal dynamin lacked the stalk regions and exists as monomer. When dynamin assembles into short collars, the GTPase domains of neighboring tetramers form functional dimers that are necessary for GTPase activity and for membrane pinching.
Based on the structure that Chappie, Schmid, Dyda and colleagues described, the scientists suggest that when the GTPase domains from different tetramers pair up the structures of the tetramers shift, making them less stable. The conversion of GTP to GDP then causes another change in shape in the tetramers, possibly through a twisting motion on the membrane. As a result, the dimers dissociate and the entire collar structure comes apart. Vesicle formation probably involves repeated cycles of collar assembly, GTP binding, GTPase domain dimerization, conversion of GTP to GDP, and disassembly of the dynamin collar. These cycles eventually twist and pinch off the membrane.
The crystal structure of the shortened dynamin has revealed other important information. For example, the protein contains three amino acids that are absolutely critical for its GTPase activity and that are conserved among all GTPases with similar functions, providing a "signature" for this group of enzymes.
"Many of the questions we've been trying to answer for the past decade were answered by this structure," says Schmid.
New questions, of course, now follow and the Schmid team is investigating.
In addition to Chappie, Schmid, and Dyda, authors of the paper, "G domain dimerization controls dynamin's assembly stimulated GTPase activity," are Sharmistha Acharya and Marilyn Leonard of Scripps Research.
The work was supported by the National Institutes of Health. X-ray diffraction data were obtained at the Advanced Photon Source, Argonne National Laboratory, which is supported by the National Institutes of Health and the U.S. Department of Energy.
Source:
Keith McKeown
Scripps Research Institute
The structure of the protein, called dynamin, is helping to answer many longstanding questions about how vesicles form, advancing knowledge of a process critical to cell survival. The findings may also have implications for designing better ways for delivering drugs.
The research was published on April 28, 2010, in an advance, online issue of the prestigious journal Nature.
The Puzzle of Pinching Off Membranes
The cell membrane typically acts as a barrier around the cell, keeping out harmful materials. But cells also need some substances to get inside.
To get past the membrane, nutrients or hormones in the bloodstream, for example, bind to specific receptors on cells membranes. The membrane then forms a pit around these bound molecules, which is squeezed into a pouch, or vesicle, that detaches from the rest of the cell membrane and carries its essential cargo into the cell. Nerve cells use this same vesicle-making mechanism, called endocytosis, to maintain signaling from one cell to another.
"Endocytosis is how cells communicate," says Sandra Schmid, chair of the Scripps Department of Cell Biology and senior author of the Nature article along with Fred Dyda at NIH. "It's critical for many biological functions from controlling blood pressure to getting rid of glucose."
Despite the importance of endocytosis, scientists have been puzzled by how cells perform this process. But they knew that at least one molecule, dynamin, played a starring role.
Dynamin belongs to a large family of enzymes called GTPases. These enzymes bind a chemical called GTP and convert it to a simpler form (GDP), releasing energy in the process. During this conversion a GTPase undergoes a change in shape, enabling it to perform a particular function - such as making vesicles.
Initially, most scientists believed that many dynamin molecules assembled long spirals on cell membranes, and that in the presence of GTP these spirals tightened, lopping off a vesicle.
But a year ago, a study published in Cell by Schmid's group challenged that view. By watching vesicle transformation through a microscope, the scientists showed that dynamin proteins only form a short collar around the cell membrane. What's more, dynamin can act alone, without the help of any other proteins.
"Dynamin is the master regulator of endocytosis," says Schmid. "It is involved at every stage of vesicle formation."
Seeing Is Believing
That study did not reveal how the dynamin collars pinch off membrane vesicles, though. Thus, Schmid and others turned their attention to dynamin's GTPase activity for clues of how it controls the process.
One way to figure out how a protein functions is to determine its structure. To this end, scientists often use a technique called X-ray crystallography, which involves making crystals of the protein of interest and then bombarding them with X-rays to see the positions of the atoms.
But dynamin is a large molecule, containing almost 1,000 amino acids, making it difficult to crystallize. To overcome the problem, about three years ago Joshua Chappie, then a graduate student in Schmid's laboratory, engineered a shorter version of dynamin that retained the same GTPase activity as the complete protein.
With this shortened protein Chappi quickly obtained crystals and then examined them by X-ray crystallography. However, the resulting data proved impossible to interpret because of a kind of double vision in the X-ray signals. Then came a breakthrough: Chappie discovered that the minimal dynamin formed dimers during its normal cycle of GTP hydrolysis.
Researchers knew that dynamin is found in cells as a group of four molecules, or a tetramer. Like a handful of Tootsie Pops™, dynamin tetramers are held together by long stalk regions with the GTPase domains protruding from their tops. However, the minimal dynamin lacked the stalk regions and exists as monomer. When dynamin assembles into short collars, the GTPase domains of neighboring tetramers form functional dimers that are necessary for GTPase activity and for membrane pinching.
Based on the structure that Chappie, Schmid, Dyda and colleagues described, the scientists suggest that when the GTPase domains from different tetramers pair up the structures of the tetramers shift, making them less stable. The conversion of GTP to GDP then causes another change in shape in the tetramers, possibly through a twisting motion on the membrane. As a result, the dimers dissociate and the entire collar structure comes apart. Vesicle formation probably involves repeated cycles of collar assembly, GTP binding, GTPase domain dimerization, conversion of GTP to GDP, and disassembly of the dynamin collar. These cycles eventually twist and pinch off the membrane.
The crystal structure of the shortened dynamin has revealed other important information. For example, the protein contains three amino acids that are absolutely critical for its GTPase activity and that are conserved among all GTPases with similar functions, providing a "signature" for this group of enzymes.
"Many of the questions we've been trying to answer for the past decade were answered by this structure," says Schmid.
New questions, of course, now follow and the Schmid team is investigating.
In addition to Chappie, Schmid, and Dyda, authors of the paper, "G domain dimerization controls dynamin's assembly stimulated GTPase activity," are Sharmistha Acharya and Marilyn Leonard of Scripps Research.
The work was supported by the National Institutes of Health. X-ray diffraction data were obtained at the Advanced Photon Source, Argonne National Laboratory, which is supported by the National Institutes of Health and the U.S. Department of Energy.
Source:
Keith McKeown
Scripps Research Institute
Scientists Find Key Protein Regulator Of Inflammation
Reporting in the journal Nature, researchers led by Emad Alnemri, Ph.D., professor of Biochemistry and Molecular Biology in the Kimmel Cancer Center at Jefferson, discovered a key protein component involved in inflammation.
The protein, AIM2 (absent in melanoma 2), is involved in the detection and reaction to dangerous cytoplasmic DNA that is produced by infection with viral or microbial pathogens, or by tissue damage. AIM2 also appears to be a tumor suppressor, and its inactivation may play a role in the development of cancer, according to Dr. Alnemri.
AIM2 belongs to a class of proteins called inflammasomes, which are multi-protein complexes that play major roles as guardians against both viral and bacterial infections. Inflammasomes also detect dangerous self-molecules associated with tissue damage.
According to Dr. Alnemri, when cells are infected with pathogens, AIM2 senses the presence of the pathogen's DNA in the cytoplasm. It then binds to the foreign DNA and causes a rapid inflammatory reaction that sends a danger signal alerting the body to the invading pathogen.
When AIM2 binds to the foreign DNA, it recruits a cytoplasmic protein called ASC. ASC and AIM2 then work together to activate caspase-1, a cysteine protease involved in the production of interleukin1 and other inflammatory cytokines that cause inflammation.
"Researchers have long sought this elusive protein that senses the presence of DNA in the cytoplasm, which is associated with pathogenic infection or the escape of undigested self-DNA into the cytoplasm," Dr. Alnemri said. "We not only identified the key protein in this process, but also discovered how this protein reacts to DNA and causes inflammation. The inflammatory response triggered when AIM2 binds to foreign DNA in the cytoplasm is the body's way of alerting other systems that there is a danger present in the cell."
According to Dr. Alnemri, the activation of AIM2 also leads to death of the infected cells, which removes the damaged cells from the body. This prevents the pathogen from replicating in the cells and spreading to other parts of the body. The fact that AIM2 can induce cell death raises the possibility that AIM2 might function as a tumor suppressor, by killing cells with damaged DNA before they transform into cancers. Inactivation of AIM2 thus might confer a growth advantage to abnormal cells and lead to the development of cancer.
"The discovery and understanding of the AIM2 inflammasome should enable scientists to design novel therapeutics that modulate its activity," Dr. Alnemri said. "Such therapeutics may be useful for the treatment of nucleic acid dependent pathogenic and autoimmune diseases, such as arthritis and systemic lupus erythematosus," Dr. Alnemri said.
Thomas Jefferson University
211 S 9th St., Ste. 310
Philadelphia
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United States
tju
The protein, AIM2 (absent in melanoma 2), is involved in the detection and reaction to dangerous cytoplasmic DNA that is produced by infection with viral or microbial pathogens, or by tissue damage. AIM2 also appears to be a tumor suppressor, and its inactivation may play a role in the development of cancer, according to Dr. Alnemri.
AIM2 belongs to a class of proteins called inflammasomes, which are multi-protein complexes that play major roles as guardians against both viral and bacterial infections. Inflammasomes also detect dangerous self-molecules associated with tissue damage.
According to Dr. Alnemri, when cells are infected with pathogens, AIM2 senses the presence of the pathogen's DNA in the cytoplasm. It then binds to the foreign DNA and causes a rapid inflammatory reaction that sends a danger signal alerting the body to the invading pathogen.
When AIM2 binds to the foreign DNA, it recruits a cytoplasmic protein called ASC. ASC and AIM2 then work together to activate caspase-1, a cysteine protease involved in the production of interleukin1 and other inflammatory cytokines that cause inflammation.
"Researchers have long sought this elusive protein that senses the presence of DNA in the cytoplasm, which is associated with pathogenic infection or the escape of undigested self-DNA into the cytoplasm," Dr. Alnemri said. "We not only identified the key protein in this process, but also discovered how this protein reacts to DNA and causes inflammation. The inflammatory response triggered when AIM2 binds to foreign DNA in the cytoplasm is the body's way of alerting other systems that there is a danger present in the cell."
According to Dr. Alnemri, the activation of AIM2 also leads to death of the infected cells, which removes the damaged cells from the body. This prevents the pathogen from replicating in the cells and spreading to other parts of the body. The fact that AIM2 can induce cell death raises the possibility that AIM2 might function as a tumor suppressor, by killing cells with damaged DNA before they transform into cancers. Inactivation of AIM2 thus might confer a growth advantage to abnormal cells and lead to the development of cancer.
"The discovery and understanding of the AIM2 inflammasome should enable scientists to design novel therapeutics that modulate its activity," Dr. Alnemri said. "Such therapeutics may be useful for the treatment of nucleic acid dependent pathogenic and autoimmune diseases, such as arthritis and systemic lupus erythematosus," Dr. Alnemri said.
Thomas Jefferson University
211 S 9th St., Ste. 310
Philadelphia
PA 19107-5506
United States
tju
Destination Arctic Seed Vault For African Seed Collection
Twenty-one boxes filled with 7,000 unique seed samples from more than 36 African nations were shipped to the Svalbard Global Seed Vault, a facility being built on a remote island in the Arctic Circle as a repository of last resort for humanity's agricultural heritage.
The vault is being built by the Norwegian government as a service to the global community, and a Rome-based international NGO, the Global Crop Diversity Trust, will fund its operation. The vault will open on 26 February 2008.
The shipment, which was sent by the Ibadan, Nigeria-based International Institute of Tropical Agriculture (IITA), consists of thousands of duplicates of unique varieties of domesticated and wild cowpea, maize, soybean, and Bambara groundnut. The seeds from the IITA genebank in Ibadan, Nigeria, were packed in 21 boxes weighing a total of 330 kg. The processing by IITA staff took several months, and the boxes were packaged over a three-day period, with 10 staff checking the accession list, reporting errors, and adjusting the inventory, as needed.
The seeds were shipped on to Oslo on route to the village of Longyearbyen on Norway's Svalbard archipelago, where the vault has been constructed in a mountain deep inside the Arctic permafrost.
"IITA's genebank houses the world's largest collection of cowpea, with over 15,000 unique varieties from 88 countries around the world," said Dr Dominique Dumet, genebank manager at IITA. "Our collection holds in-trust about 70 percent of cowpea landraces from Africa. Cowpea (also known as black-eyed pea in the USA) is a key staple in Africa, offering an inexpensive source of protein."
This month, other centers supported by the Consultative Group on International Agricultural Research (CGIAR) began packing and shipping duplicate collections from Benin, Colombia, Ethiopia, India, Kenya, Mexico, Peru, the Philippines, and Syria. Collectively, the CGIAR centers maintain 600,000 plant varieties in crop genebanks, which are widely viewed as the foundation of global efforts to conserve agricultural biodiversity.
Crop biodiversity is the raw material needed to equip crops with critical resistance to pests and diseases, and enable them to grow in harsher conditions of drought, salinity, and flooding, which will likely increase with global climate change, particularly in poor nations.
Cowpea and dozens of other crops, like cassava, yams, and millets, are known as "orphan" crops, because they receive less attention than they deserve relative to their value and importance.
According to researchers at the World Vegetable Center in Taiwan, collectively, 27 "orphan" crops with a value of $100 billion are grown on 250 million hectares (618 million acres) in developing countries.
"So called 'orphan' crops like cowpea and groundnut are not minor or insignificant crops," said Cary Fowler, executive director of the Global Crop Diversity Trust. "They are of great importance to regional food security. In addition, they are often adapted to harsh environments and are diverse in terms of their genetic, agroclimatic, and economic niches."
These crops may also vary in less obvious characteristics, such as their response to cold, heat or drought, or their ability to tolerate specific pests and diseases. Farmers and scientists continually draw on the genetic diversity held in crop collections like IITA's to ensure productive harvests.
"Our ability to endow this facility with such an impressive array of diversity is a powerful testament to the incredible work of scientists at our centers, who have been so dedicated to ensuring the survival of the world's most important crop species," said Emile Frison, Director General of Rome-based Bioversity International, which coordinates CGIAR crop diversity initiatives.
Storage of these and all the other seeds at Svalbard is intended to ensure that they will be available for bolstering food security should a manmade or natural disaster threaten agricultural systems, or even the genebanks themselves, at any point in the future.
Consultative Group on International Agricultural Research (cgiar/)
The Consultative Group on International Agricultural Research (CGIAR), established in 1971, is a strategic partnership of countries, international and regional organizations and private foundations supporting the work of 15 international agricultural research Centers. In collaboration with national agricultural research systems, civil society and the private sector, the CGIAR fosters sustainable agricultural growth through high-quality science aimed at benefiting the poor through stronger food security, better human nutrition and health, higher incomes and improved management of natural resources.
The Global Crop Diversity Trust (croptrust/)
The mission of the Trust is to ensure the conservation and availability of crop diversity for food security worldwide. Although crop diversity is fundamental to fighting hunger and to the very future of agriculture, funding is unreliable and diversity is being lost. The Trust is the only organization working worldwide to solve this problem.
Source: Jeff Haskins
CGIAR
The vault is being built by the Norwegian government as a service to the global community, and a Rome-based international NGO, the Global Crop Diversity Trust, will fund its operation. The vault will open on 26 February 2008.
The shipment, which was sent by the Ibadan, Nigeria-based International Institute of Tropical Agriculture (IITA), consists of thousands of duplicates of unique varieties of domesticated and wild cowpea, maize, soybean, and Bambara groundnut. The seeds from the IITA genebank in Ibadan, Nigeria, were packed in 21 boxes weighing a total of 330 kg. The processing by IITA staff took several months, and the boxes were packaged over a three-day period, with 10 staff checking the accession list, reporting errors, and adjusting the inventory, as needed.
The seeds were shipped on to Oslo on route to the village of Longyearbyen on Norway's Svalbard archipelago, where the vault has been constructed in a mountain deep inside the Arctic permafrost.
"IITA's genebank houses the world's largest collection of cowpea, with over 15,000 unique varieties from 88 countries around the world," said Dr Dominique Dumet, genebank manager at IITA. "Our collection holds in-trust about 70 percent of cowpea landraces from Africa. Cowpea (also known as black-eyed pea in the USA) is a key staple in Africa, offering an inexpensive source of protein."
This month, other centers supported by the Consultative Group on International Agricultural Research (CGIAR) began packing and shipping duplicate collections from Benin, Colombia, Ethiopia, India, Kenya, Mexico, Peru, the Philippines, and Syria. Collectively, the CGIAR centers maintain 600,000 plant varieties in crop genebanks, which are widely viewed as the foundation of global efforts to conserve agricultural biodiversity.
Crop biodiversity is the raw material needed to equip crops with critical resistance to pests and diseases, and enable them to grow in harsher conditions of drought, salinity, and flooding, which will likely increase with global climate change, particularly in poor nations.
Cowpea and dozens of other crops, like cassava, yams, and millets, are known as "orphan" crops, because they receive less attention than they deserve relative to their value and importance.
According to researchers at the World Vegetable Center in Taiwan, collectively, 27 "orphan" crops with a value of $100 billion are grown on 250 million hectares (618 million acres) in developing countries.
"So called 'orphan' crops like cowpea and groundnut are not minor or insignificant crops," said Cary Fowler, executive director of the Global Crop Diversity Trust. "They are of great importance to regional food security. In addition, they are often adapted to harsh environments and are diverse in terms of their genetic, agroclimatic, and economic niches."
These crops may also vary in less obvious characteristics, such as their response to cold, heat or drought, or their ability to tolerate specific pests and diseases. Farmers and scientists continually draw on the genetic diversity held in crop collections like IITA's to ensure productive harvests.
"Our ability to endow this facility with such an impressive array of diversity is a powerful testament to the incredible work of scientists at our centers, who have been so dedicated to ensuring the survival of the world's most important crop species," said Emile Frison, Director General of Rome-based Bioversity International, which coordinates CGIAR crop diversity initiatives.
Storage of these and all the other seeds at Svalbard is intended to ensure that they will be available for bolstering food security should a manmade or natural disaster threaten agricultural systems, or even the genebanks themselves, at any point in the future.
Consultative Group on International Agricultural Research (cgiar/)
The Consultative Group on International Agricultural Research (CGIAR), established in 1971, is a strategic partnership of countries, international and regional organizations and private foundations supporting the work of 15 international agricultural research Centers. In collaboration with national agricultural research systems, civil society and the private sector, the CGIAR fosters sustainable agricultural growth through high-quality science aimed at benefiting the poor through stronger food security, better human nutrition and health, higher incomes and improved management of natural resources.
The Global Crop Diversity Trust (croptrust/)
The mission of the Trust is to ensure the conservation and availability of crop diversity for food security worldwide. Although crop diversity is fundamental to fighting hunger and to the very future of agriculture, funding is unreliable and diversity is being lost. The Trust is the only organization working worldwide to solve this problem.
Source: Jeff Haskins
CGIAR
Royal Society To Honour Unsung Heroes Of Science
The Royal Society, the UK's national academy of science, announced this week that it will recognise the unsung heroes of science, technology, engineering and maths for their work and commitment in these areas with a new award. The Royal Society Hauksbee Awards will celebrate the contribution made to the UK science base by the many individuals who support these disciplines.
The call for nominations for the awards, which will be made in February 2010 as part of the Society's 350th Anniversary celebrations, is now open. Employers and senior colleagues will have until 29 May 2009 to make nominations and up to ten recipients will receive a Royal Society engraved bronze medal, scroll and ВЈ500 at a ceremony held in London.
The Royal Society will recognise and reward those in roles that support the UK science base in the following categories: schools and colleges, universities, industry and the public sector. Nominations are expected to cover roles such as laboratory technicians, teachers, teaching assistants and many more.
The awards are named after Francis Hauksbee who was Isaac Newton's laboratory assistant at the Royal Society. During his time as President, Newton appointed Hauksbee as curator and instrument maker, and Hauksbee later became a Fellow in his own right in 1705.
Professor Carol Robinson FRS, who is chair of the Hauksbee Awards Committee which will be selecting award recipients said:
"Many laboratories and science classrooms could not operate but for the dedication and skill of individuals working behind the scenes. These people are dedicated to their fields and inspire all around them. The Hauksbee Awards are a way for us to take note of the excellent work being done by these individuals and thank them for their invaluable contribution to the sciences."
For further information on making nominations for the Hauksbee Awards please visit royalsociety/hauksbee.
1.The Royal Society is an independent academy promoting the natural and applied sciences. Founded in 1660, the Society has three roles, as the UK academy of science, as a learned Society, and as a funding agency. It responds to individual demand with selection by merit, not by field. As we prepare for our 350th anniversary in 2010, we are working to achieve five strategic priorities, to:
- Invest in future scientific leaders and in innovation
- Influence policymaking with the best scientific advice
- Invigorate science and mathematics education
- Increase access to the best science internationally
- Inspire an interest in the joy, wonder and excitement of scientific discovery
Source
The Royal Society
The call for nominations for the awards, which will be made in February 2010 as part of the Society's 350th Anniversary celebrations, is now open. Employers and senior colleagues will have until 29 May 2009 to make nominations and up to ten recipients will receive a Royal Society engraved bronze medal, scroll and ВЈ500 at a ceremony held in London.
The Royal Society will recognise and reward those in roles that support the UK science base in the following categories: schools and colleges, universities, industry and the public sector. Nominations are expected to cover roles such as laboratory technicians, teachers, teaching assistants and many more.
The awards are named after Francis Hauksbee who was Isaac Newton's laboratory assistant at the Royal Society. During his time as President, Newton appointed Hauksbee as curator and instrument maker, and Hauksbee later became a Fellow in his own right in 1705.
Professor Carol Robinson FRS, who is chair of the Hauksbee Awards Committee which will be selecting award recipients said:
"Many laboratories and science classrooms could not operate but for the dedication and skill of individuals working behind the scenes. These people are dedicated to their fields and inspire all around them. The Hauksbee Awards are a way for us to take note of the excellent work being done by these individuals and thank them for their invaluable contribution to the sciences."
For further information on making nominations for the Hauksbee Awards please visit royalsociety/hauksbee.
1.The Royal Society is an independent academy promoting the natural and applied sciences. Founded in 1660, the Society has three roles, as the UK academy of science, as a learned Society, and as a funding agency. It responds to individual demand with selection by merit, not by field. As we prepare for our 350th anniversary in 2010, we are working to achieve five strategic priorities, to:
- Invest in future scientific leaders and in innovation
- Influence policymaking with the best scientific advice
- Invigorate science and mathematics education
- Increase access to the best science internationally
- Inspire an interest in the joy, wonder and excitement of scientific discovery
Source
The Royal Society
Moving Towards Greener Chemistry And Improved Pharmaceuticals
Proteins are the workhorses of our cells. They help to digest our food, are at the core of our immune system, and literally shape our body from top to toe. Proteins also play an important role in biotechnology in the form of enzymes, which are important in the creation of anything from pharmaceuticals to bread, washing powder and much more. Their possibilities are virtually without limit.
To take advantage of their great potential, a detailed understanding of the three-dimensional shape of proteins is necessary. This is normally achieved through a complicated and expensive process in the laboratory. For years, researchers have tried to replace these experiments by computer simulations.
Now, two researchers at the Department of Biology at the University of Copenhagen, Assoc. professor Thomas Hamelryck and PhD-student Wouter Boomsma, have solved an important part of the problem of modeling the three dimensional shape of proteins. After 5 years of research, they have succeeded in developing a mathematical model that incorporates knowledge from physics, probability theory and geometry to describe the structure of proteins. This has given protein researchers a valuable new tool for the improved understanding of the shape and function of proteins.
"Each individual protein has its own unique chemical composition, consisting of 20 different amino acids in various different combinations. There are an endless number of such combinations, each giving rise to its own shape. We have developed a simple mathematical model that captures these different shapes. This means that it will become easier for industry and researchers to use proteins to achieve their goals. For example in the development of green chemistry, where dangerous chemicals are replaced with protein-based products, which are more environment friendly", says Thomas Hamelryck.
Thomas also points to the fact that their computer model can have a great impact on the pharmaceutical industry.
"Proteins and illness are highly related, and most pharmaceuticals are targeted at proteins in our body. As we increase our knowledge of these proteins, the chance of finding more efficient pharmaceuticals for illnesses such as cancer, diabetes and AIDS are greatly enhanced", Thomas continues.
The two researchers at the University of Copenhagen are currently collaborating closely with partners in the biotech industry to explore these possibilities.
The study was done in collaboration with statisticians Kanti V. Mardia and Charles C. Taylor (University of Leeds, UK), physicist Jesper Ferkinghoff-Borg (DTU, Denmark), and Professor Anders Krogh (KU, Denmark).
Source: Thomas Hameryck
University of Copenhagen
To take advantage of their great potential, a detailed understanding of the three-dimensional shape of proteins is necessary. This is normally achieved through a complicated and expensive process in the laboratory. For years, researchers have tried to replace these experiments by computer simulations.
Now, two researchers at the Department of Biology at the University of Copenhagen, Assoc. professor Thomas Hamelryck and PhD-student Wouter Boomsma, have solved an important part of the problem of modeling the three dimensional shape of proteins. After 5 years of research, they have succeeded in developing a mathematical model that incorporates knowledge from physics, probability theory and geometry to describe the structure of proteins. This has given protein researchers a valuable new tool for the improved understanding of the shape and function of proteins.
"Each individual protein has its own unique chemical composition, consisting of 20 different amino acids in various different combinations. There are an endless number of such combinations, each giving rise to its own shape. We have developed a simple mathematical model that captures these different shapes. This means that it will become easier for industry and researchers to use proteins to achieve their goals. For example in the development of green chemistry, where dangerous chemicals are replaced with protein-based products, which are more environment friendly", says Thomas Hamelryck.
Thomas also points to the fact that their computer model can have a great impact on the pharmaceutical industry.
"Proteins and illness are highly related, and most pharmaceuticals are targeted at proteins in our body. As we increase our knowledge of these proteins, the chance of finding more efficient pharmaceuticals for illnesses such as cancer, diabetes and AIDS are greatly enhanced", Thomas continues.
The two researchers at the University of Copenhagen are currently collaborating closely with partners in the biotech industry to explore these possibilities.
The study was done in collaboration with statisticians Kanti V. Mardia and Charles C. Taylor (University of Leeds, UK), physicist Jesper Ferkinghoff-Borg (DTU, Denmark), and Professor Anders Krogh (KU, Denmark).
Source: Thomas Hameryck
University of Copenhagen
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