A gene crucial for embryonic development can quickly become a potent cancer promoter in adult mice after a genetic misalignment, according to researchers from Fox Chase Cancer Center, causing white blood cells to become cancerous spontaneously.
In the March 1 issue of the journal Cancer Research, the researchers detail how a gene called Dlx5 works cooperatively with a known oncogene, Akt2, to drive cancer in mice. The protein that Dlx5 encodes could be a target for drugs to slow the growth of lymphomas and other cancers in humans, they say.
"A chromosomal inversion essentially flips a segment of DNA, placing the Dlx5 gene next to an enhancer in a neighboring gene, which in turn activates a number of other nearby genes," says lead investigator Joseph Testa, Ph.D., a cancer geneticist at Fox Chase. "The result is like placing a V8 engine on a Flexible Flyer - something is going to go fast and without much control."
According to Testa, Dlx5 is basically a good gene that starts to do bad things when it moves into a dangerous neighborhood. Dxl5 is part of the homeobox family of genes, which direct the timing of events in the physical development of a growing fetus, such as when to sprout a limb, for example. In adults, such genes are almost entirely inactive.
Unfortunately, in white blood cells, such as T cells, Dlx5 moves to a region of DNA involved in the genetic rearrangement that allows immune cells to switch genes around in order to create new combinations of proteins to respond to disease threats. This recombination process allows B cells to generate antibodies and T cells to generate T cell receptors, enabling the immune system to recognize an enormous array of foreign bacteria, viruses and parasites.
In a mouse model of T cell lymphoma, the researchers found that mice bred to over-express the Akt2 gene also over-expressed Dlx5. In fact, the researchers found the chromosomal inversion that led to cancer was a feature in the majority of mice studied. One particular line of transgenic mice exhibited the inversion in 15 of 15 tumors they examined. "Genetic recombination is a frequent component of T-cell malignancies, but it is startling to see this same pattern come up repeatedly," Testa says.
In subsequent cell studies, Testa and his colleagues determined that the combined activation of both Dlx5 and Akt2 could result in increased cell growth and proliferation. While their findings are the first to assert that Dlx5 can be an oncogene, the gene has previously been implicated in a number of human endometrial and lung cancers. Moreover, the DLX5 protein was found in abundant amounts within three out of seven human lymphomas that the Fox Chase researchers examined.
According to Testa, molecules that could bind and inhibit DLX5 could provide a more useful drug for therapeutic development than could molecules that inactivate AKT2.
"The AKT family of proteins is crucial to survival in both cancerous and non-cancerous cells, so AKT2 is a potentially risky target for drug development since blocking AKT2 can also kill healthy cells," Testa says. "DLX5, however, is not generally active in healthy adult cells, so it represents a much more 'druggable' target for inhibition."
The study was funded by grants from the National Cancer Institute and the Commonwealth of Pennsylvania.
Fox Chase Cancer Center is one of the leading freestanding cancer research and treatments centers in the United States. Founded in 1904 in Philadelphia as the nation's first cancer hospital, Fox Chase became one of the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, treatment, and community outreach. For more information, visit Fox Chase's web site at fccc/.
Source: Greg Lester
Fox Chase Cancer Center
воскресенье, 24 апреля 2011 г.
New 'Asthma Gene' Could Lead To New Therapies
A gene that is strongly associated with a risk of developing childhood onset asthma was identified by an international team of scientists, whose findings are published today in the journal Nature.
In a genetic study of more than 2,000 children, scientists from the University of Michigan and colleagues from London, France and Germany found genetic markers that dramatically increase a child's risk for asthma. These markers are located on chromosome 17, and children with this marker had higher levels of a new gene called ORMDL3 in their blood, which occurs in higher amounts in children with asthma. The presence of the disease-associated version of ORMDL3 increases the risk of asthma by 60-70 percent, the study suggests.
"In terms of an asthma gene, there have been quite a few reports but not one that can be clearly reproduced in samples," said Goncalo Abecasis, associate professor at the U-M School of Public Health. "I think eventually it will lead to new therapies because it points to a specific biological molecular pathway. Once we understand the biology and we know the players, it's possible to target with specific drugs."
Childhood asthma treatments are heavily focused on allergic responses, since most children with asthma also have many allergies. The discovery of a so-called 'asthma gene' would provide a new set of mechanisms to try and modify and manage childhood asthma, Abecasis said.
"Before we finished the paper, we would have guessed (ORMDL3) would be a gene with a well-understood role in allergic responses, but that is not what we found," said Abecasis, noting that the gene has no known relation to allergic responses.
Asthma, a complex disease caused by a combination of genetic and environmental factors, is the most common chronic disease of childhood. Asthma occurs in 7-10 percent of children in the United States and one child in seven in the United Kingdom. Its prevalence differs widely among different geographic areas.
To account for the environmental factors associated with the disease, researchers structured their investigation to ensure that cases of childhood asthma were matched to children without disease from the same geographical areas.
The team of scientists, including Liming Liang, a U-M doctoral student in Abecasis' lab and co-first author on the paper, compared the genetic makeup of 994 patients with childhood onset asthma and 1,243 non-asthmatics. They looked at mutations in the building blocks that make up DNA, called nucleotides. There are mutations in around one in every 600 nucleotides, and scientists examined more than 317,000 of these mutations, known as single-nucleotide polymorphisms, to find those specific to childhood asthma. The researchers also looked at how genes were being expressed within human blood cells. The U-M was one of the major data analysis sites.
The team confirmed its findings by analyzing the genetic makeup of more than 2,000 children from Germany and more than 3,000 subjects from the United Kingdom born in 1958 and monitored until now for the presence of disease.
"This is a large study involving doctors and scientists from many countries, and we are confident that we have discovered something new and exciting about childhood asthma," said Dr. Miriam Moffatt of the National Heath and Lung Institute, Imperial College, London, and one of the first authors of the study. "These novel findings do not explain completely how asthma is caused, but they do provide a further part of the gene-environment jigsaw that makes up the disease. We and our colleagues are currently preparing even bigger studies to find other genes of smaller effect and to relate these to environmental factors that increase asthma risk."
Professor William Cookson, also of the National Heart and Lung Institute and coordinator of the study, said the results are the strongest genetic link yet to child onset asthma.
The work was funded by the Wellcome Trust, UK Medical Research Council, French Ministry of Higher Education and Research, German Ministry of Education and Research, National Genome Research Network, National Institutes of Health and the European Commission. The study is a component of the EU-funded GABRIEL Integrated Project to investigate genetic and environmental causes of asthma in the European Union. GABRIEL is coordinated by Professor William Cookson at Imperial College and Professor Erika von Mutius at the University of Munich.
For more information on Abecasis, see: sph.umich/csg/abecasis.
For more on the School of Public Health, see: sph.umich.
The University of Michigan School of Public Health has been working to promote health and prevent disease since 1941, and is consistently ranked among the top five schools in the country. Faculty and students in the school's five academic departments and dozens of collaborative centers and institutes are forging new solutions to the complex health challenges of today, including chronic disease, health care quality and finance, emerging genetic technologies, climate change, socioeconomic inequalities and their impact on health, infectious disease, and the globalization of health. Whether making new discoveries in the lab or researching and educating in the field, SPH faculty, students and alumni are deployed around the globe to promote and protect our health.
University of Michigan
412 Maynard St.
Ann Arbor, MI 48109-1399
United States
umich
In a genetic study of more than 2,000 children, scientists from the University of Michigan and colleagues from London, France and Germany found genetic markers that dramatically increase a child's risk for asthma. These markers are located on chromosome 17, and children with this marker had higher levels of a new gene called ORMDL3 in their blood, which occurs in higher amounts in children with asthma. The presence of the disease-associated version of ORMDL3 increases the risk of asthma by 60-70 percent, the study suggests.
"In terms of an asthma gene, there have been quite a few reports but not one that can be clearly reproduced in samples," said Goncalo Abecasis, associate professor at the U-M School of Public Health. "I think eventually it will lead to new therapies because it points to a specific biological molecular pathway. Once we understand the biology and we know the players, it's possible to target with specific drugs."
Childhood asthma treatments are heavily focused on allergic responses, since most children with asthma also have many allergies. The discovery of a so-called 'asthma gene' would provide a new set of mechanisms to try and modify and manage childhood asthma, Abecasis said.
"Before we finished the paper, we would have guessed (ORMDL3) would be a gene with a well-understood role in allergic responses, but that is not what we found," said Abecasis, noting that the gene has no known relation to allergic responses.
Asthma, a complex disease caused by a combination of genetic and environmental factors, is the most common chronic disease of childhood. Asthma occurs in 7-10 percent of children in the United States and one child in seven in the United Kingdom. Its prevalence differs widely among different geographic areas.
To account for the environmental factors associated with the disease, researchers structured their investigation to ensure that cases of childhood asthma were matched to children without disease from the same geographical areas.
The team of scientists, including Liming Liang, a U-M doctoral student in Abecasis' lab and co-first author on the paper, compared the genetic makeup of 994 patients with childhood onset asthma and 1,243 non-asthmatics. They looked at mutations in the building blocks that make up DNA, called nucleotides. There are mutations in around one in every 600 nucleotides, and scientists examined more than 317,000 of these mutations, known as single-nucleotide polymorphisms, to find those specific to childhood asthma. The researchers also looked at how genes were being expressed within human blood cells. The U-M was one of the major data analysis sites.
The team confirmed its findings by analyzing the genetic makeup of more than 2,000 children from Germany and more than 3,000 subjects from the United Kingdom born in 1958 and monitored until now for the presence of disease.
"This is a large study involving doctors and scientists from many countries, and we are confident that we have discovered something new and exciting about childhood asthma," said Dr. Miriam Moffatt of the National Heath and Lung Institute, Imperial College, London, and one of the first authors of the study. "These novel findings do not explain completely how asthma is caused, but they do provide a further part of the gene-environment jigsaw that makes up the disease. We and our colleagues are currently preparing even bigger studies to find other genes of smaller effect and to relate these to environmental factors that increase asthma risk."
Professor William Cookson, also of the National Heart and Lung Institute and coordinator of the study, said the results are the strongest genetic link yet to child onset asthma.
The work was funded by the Wellcome Trust, UK Medical Research Council, French Ministry of Higher Education and Research, German Ministry of Education and Research, National Genome Research Network, National Institutes of Health and the European Commission. The study is a component of the EU-funded GABRIEL Integrated Project to investigate genetic and environmental causes of asthma in the European Union. GABRIEL is coordinated by Professor William Cookson at Imperial College and Professor Erika von Mutius at the University of Munich.
For more information on Abecasis, see: sph.umich/csg/abecasis.
For more on the School of Public Health, see: sph.umich.
The University of Michigan School of Public Health has been working to promote health and prevent disease since 1941, and is consistently ranked among the top five schools in the country. Faculty and students in the school's five academic departments and dozens of collaborative centers and institutes are forging new solutions to the complex health challenges of today, including chronic disease, health care quality and finance, emerging genetic technologies, climate change, socioeconomic inequalities and their impact on health, infectious disease, and the globalization of health. Whether making new discoveries in the lab or researching and educating in the field, SPH faculty, students and alumni are deployed around the globe to promote and protect our health.
University of Michigan
412 Maynard St.
Ann Arbor, MI 48109-1399
United States
umich
EPA Orders Cleanup Of New PCB Contamination Found At Fields Brook Superfund Site, USA
U.S. Environmental Protection Agency Region 5 has directed Millennium Inorganic Chemicals, Ashtabula, Ohio, to address newly discovered PCB contamination in Fields Brook, which flows into northeast Ohio's Ashtabula River, and eventually Lake Erie.
Fields Brook is on the Superfund National Priorities List. During 1999 - 2001, cleanup activities were conducted across nearly four miles of the brook and at six nearby industrial sites. The new contamination, a pool of heat transfer fluid containing PCBs, was discovered in September during ongoing environmental monitoring.
While plans are being finalized to investigate this newly identified contamination, the Fields Brook channel has been rerouted around the problem area. The work will be performed under the terms of a unilateral administrative order issued to Millennium. A Detroit-based EPA Superfund emergency response team will monitor the work of Millennium's contractors.
PCBs (polychlorinated biphenyls) are a group of toxic chemicals that were widely used as coolants, insulators and lubricants. PCBs are of concern because they concentrate in the food chain resulting in health hazards to people, fish and wildlife. Congress banned the manufacture of new PCBs in 1976 and PCBs still in use are strictly regulated.
epa
Fields Brook is on the Superfund National Priorities List. During 1999 - 2001, cleanup activities were conducted across nearly four miles of the brook and at six nearby industrial sites. The new contamination, a pool of heat transfer fluid containing PCBs, was discovered in September during ongoing environmental monitoring.
While plans are being finalized to investigate this newly identified contamination, the Fields Brook channel has been rerouted around the problem area. The work will be performed under the terms of a unilateral administrative order issued to Millennium. A Detroit-based EPA Superfund emergency response team will monitor the work of Millennium's contractors.
PCBs (polychlorinated biphenyls) are a group of toxic chemicals that were widely used as coolants, insulators and lubricants. PCBs are of concern because they concentrate in the food chain resulting in health hazards to people, fish and wildlife. Congress banned the manufacture of new PCBs in 1976 and PCBs still in use are strictly regulated.
epa
Blood Protein Offers Clues To Heart Attack In Healthy People
We've all wondered how a seemingly healthy person can actually be at high risk for heart disease or a heart attack. Now researchers have uncovered a new clue to this mystery. The culprit: myeloperoxidase (MPO), a protein secreted by white blood cells that both signals inflammation and releases a bleach-like substance that damages the cardiovascular system.
Although MPO is intended to kill harmful bacteria, it may instead inflame the body's arteries and cripple protective substances in the blood, according to a study published in the July 10, 2007, issue of the Journal of the American College of Cardiology (JACC). As a result, long before conventional risk factors set off alarms, elevated MPO levels signal that harmful plaque has been building up.
"We were surprised to find that many years before a cardiovascular event actually occurs, MPO is increased," said Matthijs Boekholdt, M.D., Ph.D., a resident in cardiology at Academic Medical Center in Amsterdam, the Netherlands. "This could open up completely new areas of research and diagnosis. As we learn more about these processes, we hope to be able to identify 'vulnerable blood' as a reliable tool for detecting vulnerable patients."
Not only does MPO change low-density-lipoprotein (LDL) cholesterol into a harmful oxidized form that can cause atherosclerosis, the "bleach" produced by MPO damages the arteries directly, causing cell death and erosion of the arterial lining, a process that can create unstable plaques. MPO also hampers the protective effects of high-density-lipoprotein (HDL) cholesterol and reduces the availability of nitric oxide, a natural chemical that relaxes the blood vessels.
Earlier studies in patients with chest pain and heart disease have shown that elevated levels of MPO identify those at highest risk for a heart attack. "The novelty of the present study is that it is the first large-scale study to examine the relationship of MPO to cardiovascular risk in apparently healthy individuals," Dr. Boekholdt said.
For the study Dr. Boekholdt and colleagues recruited healthy people living in Norfolk, United Kingdom, between 1993 and 1997, as part of a larger community-based research program known as the European Prospective Investigation Into Cancer and Nutrition (EPIC). They took baseline blood samples from each participant and froze the samples for future analysis.
After an average of eight years, 1,138 EPIC-Norfolk participants had been admitted to the hospital or died from the effects of coronary artery disease (CAD), including heart attack. The researchers matched these patients with study participants who remained healthy throughout the follow-up period, selecting those of the same gender and similar ages and enrollment times.
The average blood levels of MPO were significantly higher in those who developed heart disease than in those who remained healthy. In fact, when MPO levels were divided into four groups, patients in the highest fourth were 1.49 times as likely as those in the lowest fourth to develop CAD or have a heart attack. When traditional risk factors blood pressure, LDL and HDL cholesterol levels, body mass index, smoking and diabetes were taken into account, an MPO level in the highest fourth increased the risk of heart disease by 1.36 times.
Equally important, elevated MPO levels signaled increased risk even in those with acceptable levels of LDL cholesterol, HDL cholesterol or C-reactive protein, a widely acknowledged marker of inflammation.
"MPO levels help to identify individuals at increased risk for CAD when traditional risk screening fails," Dr. Boekholdt said.
The search for blood tests to help identify patients at risk for heart attack is a very important one, said Christopher Cannon, M.D., F.A.C.C., who did not participate in the study and is an associate professor of medicine at Harvard Medical School, Boston, MA. "One fascinating aspect of this study is that this marker of inflammation precedes by nearly a decade the development of clinical coronary disease," he said. "This suggests MPO could be used to catch the disease in a very early stage and help in true prevention of CAD.
"Another interesting aspect of MPO is that it may be a marker for unstable plaque. Even more than the number or severity of coronary plaques, we want to know the risk of plaque rupture, and this evolving new marker may help in that regard. More study is needed, but among the hundreds of markers tested to date, MPO looks like a "keeper" that will one day become part of clinical care," Dr. Cannon said.
Researchers are continuing to assess the value of MPO in different patient groups as well as in relation to other biomarkers, Dr. Boekholdt said. Key questions include whether, and under what circumstances, MPO should be added to the laboratory tests used to screen for cardiovascular disease, and whether blocking MPO could prevent cardiovascular disease.
The EPIC-Norfolk study is supported by program grants from the Medical Research Council UK and Cancer Research UK, with additional support from the European Union, Stroke Association, British Heart Foundation, and the Wellcome Trust. Some of the measurements in this study were supported by Wyeth. One of the study's authors, Stanley L. Hazen, M.D., Ph.D., is named as a co-inventor on pending patents filed by the Cleveland Clinic Foundation relating to the use of myeloperoxidase as a biomarker for cardiovascular disease.
The American College of Cardiology is leading the way to optimal cardiovascular care and disease prevention. The College is a 34,000-member nonprofit medical society and bestows the credential Fellow of the American College of Cardiology upon physicians who meet its stringent qualifications. The College is a leader in the formulation of health policy, standards and guidelines, and is a staunch supporter of cardiovascular research. The ACC provides professional education and operates national registries for the measurement and improvement of quality care. More information about the association is available online at acc.
The American College of Cardiology (ACC) provides these news reports of clinical studies published in the Journal of the American College of Cardiology as a service to physicians, the media, the public and other interested parties. However, statements or opinions expressed in these reports reflect the view of the author(s) and do not represent official policy of the ACC unless stated so.
American College of Cardiology (ACC)
9111 Old Georgetown Rd.
Bethesda, MD 20814
United States
acc
Although MPO is intended to kill harmful bacteria, it may instead inflame the body's arteries and cripple protective substances in the blood, according to a study published in the July 10, 2007, issue of the Journal of the American College of Cardiology (JACC). As a result, long before conventional risk factors set off alarms, elevated MPO levels signal that harmful plaque has been building up.
"We were surprised to find that many years before a cardiovascular event actually occurs, MPO is increased," said Matthijs Boekholdt, M.D., Ph.D., a resident in cardiology at Academic Medical Center in Amsterdam, the Netherlands. "This could open up completely new areas of research and diagnosis. As we learn more about these processes, we hope to be able to identify 'vulnerable blood' as a reliable tool for detecting vulnerable patients."
Not only does MPO change low-density-lipoprotein (LDL) cholesterol into a harmful oxidized form that can cause atherosclerosis, the "bleach" produced by MPO damages the arteries directly, causing cell death and erosion of the arterial lining, a process that can create unstable plaques. MPO also hampers the protective effects of high-density-lipoprotein (HDL) cholesterol and reduces the availability of nitric oxide, a natural chemical that relaxes the blood vessels.
Earlier studies in patients with chest pain and heart disease have shown that elevated levels of MPO identify those at highest risk for a heart attack. "The novelty of the present study is that it is the first large-scale study to examine the relationship of MPO to cardiovascular risk in apparently healthy individuals," Dr. Boekholdt said.
For the study Dr. Boekholdt and colleagues recruited healthy people living in Norfolk, United Kingdom, between 1993 and 1997, as part of a larger community-based research program known as the European Prospective Investigation Into Cancer and Nutrition (EPIC). They took baseline blood samples from each participant and froze the samples for future analysis.
After an average of eight years, 1,138 EPIC-Norfolk participants had been admitted to the hospital or died from the effects of coronary artery disease (CAD), including heart attack. The researchers matched these patients with study participants who remained healthy throughout the follow-up period, selecting those of the same gender and similar ages and enrollment times.
The average blood levels of MPO were significantly higher in those who developed heart disease than in those who remained healthy. In fact, when MPO levels were divided into four groups, patients in the highest fourth were 1.49 times as likely as those in the lowest fourth to develop CAD or have a heart attack. When traditional risk factors blood pressure, LDL and HDL cholesterol levels, body mass index, smoking and diabetes were taken into account, an MPO level in the highest fourth increased the risk of heart disease by 1.36 times.
Equally important, elevated MPO levels signaled increased risk even in those with acceptable levels of LDL cholesterol, HDL cholesterol or C-reactive protein, a widely acknowledged marker of inflammation.
"MPO levels help to identify individuals at increased risk for CAD when traditional risk screening fails," Dr. Boekholdt said.
The search for blood tests to help identify patients at risk for heart attack is a very important one, said Christopher Cannon, M.D., F.A.C.C., who did not participate in the study and is an associate professor of medicine at Harvard Medical School, Boston, MA. "One fascinating aspect of this study is that this marker of inflammation precedes by nearly a decade the development of clinical coronary disease," he said. "This suggests MPO could be used to catch the disease in a very early stage and help in true prevention of CAD.
"Another interesting aspect of MPO is that it may be a marker for unstable plaque. Even more than the number or severity of coronary plaques, we want to know the risk of plaque rupture, and this evolving new marker may help in that regard. More study is needed, but among the hundreds of markers tested to date, MPO looks like a "keeper" that will one day become part of clinical care," Dr. Cannon said.
Researchers are continuing to assess the value of MPO in different patient groups as well as in relation to other biomarkers, Dr. Boekholdt said. Key questions include whether, and under what circumstances, MPO should be added to the laboratory tests used to screen for cardiovascular disease, and whether blocking MPO could prevent cardiovascular disease.
The EPIC-Norfolk study is supported by program grants from the Medical Research Council UK and Cancer Research UK, with additional support from the European Union, Stroke Association, British Heart Foundation, and the Wellcome Trust. Some of the measurements in this study were supported by Wyeth. One of the study's authors, Stanley L. Hazen, M.D., Ph.D., is named as a co-inventor on pending patents filed by the Cleveland Clinic Foundation relating to the use of myeloperoxidase as a biomarker for cardiovascular disease.
The American College of Cardiology is leading the way to optimal cardiovascular care and disease prevention. The College is a 34,000-member nonprofit medical society and bestows the credential Fellow of the American College of Cardiology upon physicians who meet its stringent qualifications. The College is a leader in the formulation of health policy, standards and guidelines, and is a staunch supporter of cardiovascular research. The ACC provides professional education and operates national registries for the measurement and improvement of quality care. More information about the association is available online at acc.
The American College of Cardiology (ACC) provides these news reports of clinical studies published in the Journal of the American College of Cardiology as a service to physicians, the media, the public and other interested parties. However, statements or opinions expressed in these reports reflect the view of the author(s) and do not represent official policy of the ACC unless stated so.
American College of Cardiology (ACC)
9111 Old Georgetown Rd.
Bethesda, MD 20814
United States
acc
Peering Into The Shadow World Of RNA
The popular view is that DNA and genes control everything of importance in biology. The genome rules all of life, it is thought.
Increasingly, however, scientists are realizing that among the diverse forms of RNA, a kind of mirror molecule derived from DNA, many interact with each other and with genes directly to manage the genome from behind the scenes.
In particular, RNA produced by the vast stretches of DNA that do not code for any genes - long considered 'junk' DNA - may in fact be serving vital duty by governing important aspects of gene expression. This type of RNA is called non-coding RNA, meaning that although it may be biologically active, it does not carry the instructions for producing any protein in the body.
The importance of better understanding these non-coding forms of RNA is underscored by the fact that they are known to play roles in such critical processes as embryonic development, cell and tissue differentiation, and cancer formation.
A review of current research in this still-developing area of biology, authored by Kazuko Nishikura, Ph.D., a professor in the Gene Expression and Regulation Program at The Wistar Institute, appears in the December issue of the journal Nature Reviews Molecular Cell Biology (nature/nrm/journal/v7/n12/full/nrm2061.html).
"The essence of gene regulation occurs, of course, at the level of gene transcription," Nishikura says. "Cellular machinery transcribes genetic DNA into messenger RNA from which the proteins of the body are produced. In the last several years, however, scientists investigating the biological meaning of other forms of RNA that don't code for proteins have discovered that they oversee another, more subtle level of genome control."
br>
Nishikura's own research has for many years explored RNA editing mechanisms. In particular, she has studied an enzyme called ADAR that converts specific occurrences of a basic RNA building-block molecule called adenosine into another called inosine. In her laboratory, this simple substitution has been seen to have significant biological effects, altering the expression of certain neurotransmitter genes, for example.
Last year, this work converged with that of researchers investigating an extensive family of small molecules called microRNAs, or miRNAs, non-coding forms of RNA that appear to target and inactivate particular sets of messenger RNAs, thus preventing them from producing protein and effectively silencing the group of genes from which they were transcribed. In that study, Nishikura found that that precursor miRNAs, like messenger RNAs, are themselves subject to specific RNA editing, the result of which is to suppress - or perhaps refocus - miRNA expression and activity (nature/nsmb/journal/v13/n1/full/nsmb1041.html).
"MicroRNAs often target a specific set of genes," Nishikura notes. "But when editing occurs, they may target a completely different set of genes."
In recent years, Nishikura says, a growing number of scientists are discovering other links between RNA editing and the activities of different forms of non-coding RNA.
br>
"We used to believe there were only a limited number of RNA editing sites," she says, 2but now we think there may be as many as 20,000 sites involving perhaps 3,000 genes. Interestingly, most of the editing sites correlate with non-coding regions of DNA, the so-called junk DNA."
One reason for this, Nishikura and others speculate, may be that the majority of these non-coding regions are composed of repetitive sequences of DNA called transposons. The largest class of transposons, known as retrotransposons, have the remarkable ability to copy themselves into RNA, translate themselves back into DNA, and then reinsert themselves back into the DNA at the new location. If their insertion spot happens to be within the coding region for a vital gene, the result can be destruction of the gene, leading to birth defects and genetic disease.
Over evolutionary history, this ability of transposons to copy themselves to new locations has helped them to dramatically expand their representation in the mammalian genome.
"Transposons occupy as much as half of our entire genome, and they can be dangerous," Nishikura says. "As a result, mechanisms have arisen through evolution to suppress their activity. This is particularly true in the egg and sperm, where maintenance of the genome's integrity is critical."
One of these suppression mechanisms involves short interfering RNA, or siRNA, a form of non-coding RNA that specifically targets and inactivates the stretch of DNA from which it originated. In the case of transposons, this would effectively limit their ability to act, thus protecting the genome from potential disruption.
Research in the Nishikura laboratory is supported in part by grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health.
The Wistar Institute is an international leader in biomedical research, with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. Discoveries at Wistar have led to the creation of the rubella vaccine that eradicated the disease in the U.S., rabies vaccines used worldwide, and a new rotavirus vaccine approved in 2006. Wistar scientists have also identified many cancer genes and developed monoclonal antibodies and other important research tools. Today, Wistar is home to eminent melanoma researchers and pioneering scientists working on experimental vaccines against flu, HIV, and other diseases. The Institute works actively to transfer its inventions to the commercial sector to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today's Discoveries - Tomorrow's Cures. On the web at wistar/.
Contact: Franklin Hoke
The Wistar Institute
Increasingly, however, scientists are realizing that among the diverse forms of RNA, a kind of mirror molecule derived from DNA, many interact with each other and with genes directly to manage the genome from behind the scenes.
In particular, RNA produced by the vast stretches of DNA that do not code for any genes - long considered 'junk' DNA - may in fact be serving vital duty by governing important aspects of gene expression. This type of RNA is called non-coding RNA, meaning that although it may be biologically active, it does not carry the instructions for producing any protein in the body.
The importance of better understanding these non-coding forms of RNA is underscored by the fact that they are known to play roles in such critical processes as embryonic development, cell and tissue differentiation, and cancer formation.
A review of current research in this still-developing area of biology, authored by Kazuko Nishikura, Ph.D., a professor in the Gene Expression and Regulation Program at The Wistar Institute, appears in the December issue of the journal Nature Reviews Molecular Cell Biology (nature/nrm/journal/v7/n12/full/nrm2061.html).
"The essence of gene regulation occurs, of course, at the level of gene transcription," Nishikura says. "Cellular machinery transcribes genetic DNA into messenger RNA from which the proteins of the body are produced. In the last several years, however, scientists investigating the biological meaning of other forms of RNA that don't code for proteins have discovered that they oversee another, more subtle level of genome control."
br>
Nishikura's own research has for many years explored RNA editing mechanisms. In particular, she has studied an enzyme called ADAR that converts specific occurrences of a basic RNA building-block molecule called adenosine into another called inosine. In her laboratory, this simple substitution has been seen to have significant biological effects, altering the expression of certain neurotransmitter genes, for example.
Last year, this work converged with that of researchers investigating an extensive family of small molecules called microRNAs, or miRNAs, non-coding forms of RNA that appear to target and inactivate particular sets of messenger RNAs, thus preventing them from producing protein and effectively silencing the group of genes from which they were transcribed. In that study, Nishikura found that that precursor miRNAs, like messenger RNAs, are themselves subject to specific RNA editing, the result of which is to suppress - or perhaps refocus - miRNA expression and activity (nature/nsmb/journal/v13/n1/full/nsmb1041.html).
"MicroRNAs often target a specific set of genes," Nishikura notes. "But when editing occurs, they may target a completely different set of genes."
In recent years, Nishikura says, a growing number of scientists are discovering other links between RNA editing and the activities of different forms of non-coding RNA.
br>
"We used to believe there were only a limited number of RNA editing sites," she says, 2but now we think there may be as many as 20,000 sites involving perhaps 3,000 genes. Interestingly, most of the editing sites correlate with non-coding regions of DNA, the so-called junk DNA."
One reason for this, Nishikura and others speculate, may be that the majority of these non-coding regions are composed of repetitive sequences of DNA called transposons. The largest class of transposons, known as retrotransposons, have the remarkable ability to copy themselves into RNA, translate themselves back into DNA, and then reinsert themselves back into the DNA at the new location. If their insertion spot happens to be within the coding region for a vital gene, the result can be destruction of the gene, leading to birth defects and genetic disease.
Over evolutionary history, this ability of transposons to copy themselves to new locations has helped them to dramatically expand their representation in the mammalian genome.
"Transposons occupy as much as half of our entire genome, and they can be dangerous," Nishikura says. "As a result, mechanisms have arisen through evolution to suppress their activity. This is particularly true in the egg and sperm, where maintenance of the genome's integrity is critical."
One of these suppression mechanisms involves short interfering RNA, or siRNA, a form of non-coding RNA that specifically targets and inactivates the stretch of DNA from which it originated. In the case of transposons, this would effectively limit their ability to act, thus protecting the genome from potential disruption.
Research in the Nishikura laboratory is supported in part by grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health.
The Wistar Institute is an international leader in biomedical research, with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. Discoveries at Wistar have led to the creation of the rubella vaccine that eradicated the disease in the U.S., rabies vaccines used worldwide, and a new rotavirus vaccine approved in 2006. Wistar scientists have also identified many cancer genes and developed monoclonal antibodies and other important research tools. Today, Wistar is home to eminent melanoma researchers and pioneering scientists working on experimental vaccines against flu, HIV, and other diseases. The Institute works actively to transfer its inventions to the commercial sector to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today's Discoveries - Tomorrow's Cures. On the web at wistar/.
Contact: Franklin Hoke
The Wistar Institute
EuropaBio Acknowledges Need For Review Of Laboratory Animal Protection Directive
EuropaBio, the European Biotech Industry Association, acknowledges the review of Directive 86/609, the laboratory animal protection Directive, but calls for a reduction of the bureaucratic burden the Directive places on SMEs. The legislation updates the rules and standards for breeding, use, housing and care of laboratory animals which were adopted over twenty years ago and now need to reflect advances in science and technology.
EuropaBio notes the great contribution biotechnology has made to the European Commission's "three Rs" principle of replacing, reducing, and refining animal testing and would like to see this work better supported. The biotechnology industry has promoted the use of alternative cell tests for toxicology and is increasingly using pharmocogenetics and genomics to better understand the cause of disease rather than use animals in the research and development of new therapies. Cell culture is currently the most successful and promising alternative to animal use. For example, cultured cells have been developed to create monoclonal antibodies, which previously required animals to undergo a procedure likely to cause pain and distress. Cell culture can supplement and could, one day, replace much of the animal testing done to assess the safety and efficacy of medicines. However, it is worth noting that current legislation requires an animal test to be carried out to prove safety.
"We fully support the highest standards for animal care and animal welfare but we are concerned with the bureaucracy proposed by the European Commission Directive, which does not improve the welfare of animals but disproportionately burdens small and medium enterprises" said EuropaBio's Secretary General Willy De Greef.
It is important for the competitiveness of the healthcare biotechnology industry that the European Commission recognizes and quantifies the extent of the bureaucratic burden that the new Directive places on innovative SMEs, especially in the area of ethical advice on the housing and care of laboratory animals. EuropaBio supports ethical review but calls on the European Commission to re-examine the bureaucracy involved and the potential for needless duplication which could hinder badly needed research.
About EuropaBio
EuropaBio is the European Association for Bioindustries, solely and uniquely bringing together bioscience companies from all fields of research and development, testing, manufacturing and distribution of biotechnology products. It has 79 corporate members operating worldwide, 5 associate members, 6 BioRegions and 25 national biotechnology associations representing some 1800 small and medium sized enterprises involved in research. Its mission is to promote an innovative and dynamic biotechnology-based industry in Europe. europabio/
EuropaBio is a founding trade association of the EPAA, the European partnership for alternative approaches to animal testing, a joint initiative between industry and the European Commission.
epaa.eu
EuropaBio notes the great contribution biotechnology has made to the European Commission's "three Rs" principle of replacing, reducing, and refining animal testing and would like to see this work better supported. The biotechnology industry has promoted the use of alternative cell tests for toxicology and is increasingly using pharmocogenetics and genomics to better understand the cause of disease rather than use animals in the research and development of new therapies. Cell culture is currently the most successful and promising alternative to animal use. For example, cultured cells have been developed to create monoclonal antibodies, which previously required animals to undergo a procedure likely to cause pain and distress. Cell culture can supplement and could, one day, replace much of the animal testing done to assess the safety and efficacy of medicines. However, it is worth noting that current legislation requires an animal test to be carried out to prove safety.
"We fully support the highest standards for animal care and animal welfare but we are concerned with the bureaucracy proposed by the European Commission Directive, which does not improve the welfare of animals but disproportionately burdens small and medium enterprises" said EuropaBio's Secretary General Willy De Greef.
It is important for the competitiveness of the healthcare biotechnology industry that the European Commission recognizes and quantifies the extent of the bureaucratic burden that the new Directive places on innovative SMEs, especially in the area of ethical advice on the housing and care of laboratory animals. EuropaBio supports ethical review but calls on the European Commission to re-examine the bureaucracy involved and the potential for needless duplication which could hinder badly needed research.
About EuropaBio
EuropaBio is the European Association for Bioindustries, solely and uniquely bringing together bioscience companies from all fields of research and development, testing, manufacturing and distribution of biotechnology products. It has 79 corporate members operating worldwide, 5 associate members, 6 BioRegions and 25 national biotechnology associations representing some 1800 small and medium sized enterprises involved in research. Its mission is to promote an innovative and dynamic biotechnology-based industry in Europe. europabio/
EuropaBio is a founding trade association of the EPAA, the European partnership for alternative approaches to animal testing, a joint initiative between industry and the European Commission.
epaa.eu
From Engineering Solutions To Extending Human Healthspan To Developing Socially Assistive Robotics For Physical And Cognitive Health
The National Academies Keck FUTURES INITIATIVE has announced the recipients of its 2007 FUTURES grants, each awarded to support interdisciplinary research on aging and healthspan -- the period of life that is free from serious or chronic illness. The 15 projects chosen represent a wide range of approaches to such research, which was the subject of the fifth annual FUTURES conference, "The Future of Human Healthspan: Demography, Evolution, Medicine, and Bioengineering," held last November in Irvine, Calif. A summary of the conference, which explores challenges in this field and possible solutions, is available online at keckfutures.
John W. Rowe, M.D., professor of health policy and management, Columbia University, New York City, and the conference chair, said, "We received many bold and innovative proposals and believe we have selected the most promising research projects to pursue."
These competitive seed grants aim to fill a critical gap for research on new ideas. Major federal funding programs do not typically provide support in areas that are considered risky or unusual. The FUTURES grants allow researchers to start recruiting students and postdoctoral fellows, purchasing equipment, and acquiring preliminary data - all of which can position the researchers to compete for larger awards from other public and private sources.
Established through a $40 million grant from the W.M. Keck Foundation in 2003, the National Academies Keck FUTURES INITIATIVE is a 15-year effort to enhance communication among researchers, funding agencies, universities, and the general public - with the objective of stimulating interdisciplinary research at the most exciting frontiers. The National Academies and the W.M. Keck Foundation believe considerable scientific progress and social benefit will be achieved by providing a counterbalance to the tendency to isolate research within academic fields. The FUTURES INITIATIVE is designed to enable researchers from different disciplines to focus on new questions and entirely new research, and to encourage better communication among scientists as well as between the scientific community and the public.
The award recipients and their grant research topics are:
STEVEN AUSTAD, University of Texas Health Science Center, San Antonio
DAVID J. WATERS, Purdue University, West Lafayette, Ind.
WORKSHOP ON THE DEVELOPMENT OF DOGS AS ANIMAL MODELS FOR THE STUDY OF EXTENDED HEALTHSPAN - $25,000
These researchers will hold a workshop with experts in basic aging research, canine genomics, epidemiology, pathology, and the assessment of canine health, to develop a research plan to study dogs and breed differences for animal models of extended healthspan.
LAZELLE BENEFIELD, University of Oklahoma Health Sciences Center, Oklahoma City
GEORGE DEMIRIS, University of Washington, Seattle
TAMARA HAYES, JEFFREY KAYE, and MISHA PAVEL, Oregon Health & Science University, Portland
MARGARET PERKINSON, St. Louis University
ELAINE WITTENBERG-LYLES, University of North Texas, Denton
TECHNOLOGY-ENHANCED INTERVENTIONS FOR DISTANCE CAREGIVING OF OLDER ADULTS: AN INTERDISCIPLINARY APPROACH - $50,000
This project will explore information and communication technology solutions to support long-distance caregiving. The researchers will develop the long-term research agenda to assess human-technology interface within an aging-in-place model.
BAMBI BREWER, SUJATA PRADHAN, and ANTHONY DELITTO, University of Pittsburgh
ROBOTIC ASSESSMENT FOR QUANTIFICATION OF PRECLINICAL SYMPTOMS OF NEURODEGENERATIVE DISEASE - $75,000
These researchers will use robotic technology to develop methods to measure early symptoms of degenerative diseases like Parkinson's disease. Such tools could increase the human healthspan by accelerating the development of drug treatment and allowing early diagnosis of these diseases once effective treatment is available.
EILEEN CRIMMINS, University of Southern California, Los Angeles
HUMAN LIFESPAN AND HEALTHSPAN ACROSS TIME AND SPACE - $75,000
This project will estimate the healthspan or life without physiological dysregulation and impaired functioning in a number of populations that span time and space. The information gathered will be used in models that clarify the effects of changing physiological, social, and behavioral characteristics on future healthspan.
DIDDAHALLY GOVINDARAJU, Boston University School of Medicine
STEVE N. AUSTAD, University of Texas Health Science Center, San Antonio
NIR BARZILAI, Albert Einstein College of Medicine, Bronx, New York City
CHARLES LEE, Harvard Medical School, Cambridge, Mass.
COPY NUMBER VARIATION AND EXCEPTIONAL HUMAN HEALTHSPAN: THE ASHKENAZI CENTENARIANS - $87,500
Human genomic length variation ranging from 500bp to 5 Mb, also known as structural or copy number variation (CNV), has been shown to influence complex traits including longevity and diseases. These researchers will investigate this influence by a genome-wide survey of CNVs in relation to longevity among the Ashkenazi centenarians.
CHRISTINE GRANT, North Carolina State University, Raleigh
ANATOLI I YASHIN, KEITH MEADOR, and ELIZABETH ANN GERKEN HOOTEN, Duke University, Durham, N.C.
KHALED SALEH, University of Virginia, Charlottesville
SARA PECKHAM, Wellness Consultant, Cleveland
PARADIGM SHIFT TOWARD POSITIVE HEALTH AND HEALTHSPAN OUTCOMES - $50,000
This project will bring together experts from many fields including orthopedic medicine, biomedicine, and spiritual, wellness, to focus on how orthopedic events will enhance orthopedic medicine and foster health care personnel diversity, facilitating culturally competent care.
SCOTT HOFER, Oregon State University, Corvallis
JEFFREY KAYE, Oregon Health and Science University, Portland
ILENE C. SIEGLER, Duke University, Durham, N.C.
AVRON SPIRO, Boston University
HEALTH AND HEALTHSPAN IN LONGITUDINAL STUDIES OF AGING - $75,000
These researchers will hold a conference to better understand age-related health changes by evaluating measurement and modeling approaches. Using current longitudinal studies of aging, participants will compare the various models, measures, and methods of assessing health and provide an empirical basis for harmonizing existing measures, suggesting novel ones, and eventually integrating health information from new and ongoing longitudinal studies across disciplines.
KENNETH MANTON, Duke University, Durham, N.C.
PLATEAUS IN HUMAN MORTALITY AND DISABILITY DYNAMICS AT ADVANCED AGES - $87,500
This project will examine data from National Long-Term Care Surveys from 1982 to 2004 with data for linked Medicare Part B files for the same dates to see if the age trajectory of human mortality and disability processes reaches a plateau or even declines, above age 95.
MAJA MATARIC and CALEB FINCH, University of Southern California, Los Angeles
SOCIALLY ASSISTIVE ROBOTICS FOR THE PHYSICAL AND COGNITIVE HEALTH - $75,000
Socially assistive robotics (SAR) -- autonomous, intelligent, and companionable technology -- has the potential to positively impact the human healthspan. These researchers will develop and test SAR systems that provide individualized physical and cognitive exercises for improving motivation and function, in a socially engaging context, through social (not physical) human-machine interaction.
RICHARD MILLER, University of Michigan, Ann Arbor
STEVEN AUSTAD, University of Texas, San Antonio
JUDITH CAMPISI, Lawrence Berkeley National Laboratory, Berkeley, Calif.
CALEB FINCH, University of Southern California, Los Angeles
LINDA MILLER, Nature Publishing Group, New York City
CHRISTOPHER K. PATIL, Lawrence Berkeley National Laboratory, Berkeley, Calif.
WOODRING ERIK WRIGHT, University of Texas Southwestern Medical Center, Dallas
COMPARATIVE BIOGERONTOLOGY INITIATIVE - $75,000
These researchers will hold two meetings with senior scholars to develop a plan to test hypotheses about biological factors that control lifespan and healthspan, and compare tissues from multiple species of animals. The scholars are pathologists, comparative physiologists, methodologists, statisticians, and experts in the biology of aging.
STEVEN ORZACK, Fresh Pond Research Institute, Cambridge, Mass.
DIDDAHALLY R. GOVINDARAJU, Boston University School of Medicine
SHRIPAD TULJAPURKAR, Stanford University, Stanford, Calif.
TIM COULSON, Imperial College, London
SIGNATURES OF HEALTHSPAN IN HUMANS - $75,000
These researchers will study the causal basis for differences in human healthspan by using "signatures" and health trajectories, and assessing the dynamic nature of heterogeneity of healthspan.
CORINNA ROSS, University of Texas Health Science Center, San Antonio
SARA ESPINOZA, University of Texas, San Antonio
DEVELOPMENT OF A SMALL PRIMATE MODEL OF FRAILTY - $25,000
Frailty has been defined as a wasting syndrome characterized by weight loss, fatigue, weakness, and vulnerability to stressors that predisposes them to increased risk of morbidity and mortality. These researchers will convene a group of experts to explore the development of a small primate model of frailty.
RICHARD SPROTT, The Ellison Medical Foundation, Bethesda, Md.
CREATING A CENTER FOR MODELS FOR HEALTHSPAN RESEARCH - $75,000
There are currently no accepted models for healthspan research. A universally accessible center for model development and maintenance would make an enormous contribution to this essential research. This project is to convene a group of experts to develop guidelines for healthspan models.
CATHERINE WOLKOW, National Institute on Aging Intramural Research Program, Bethesda, Md.
NAN JOKERST, Duke University, Durham, N.C.
CRAIG S. ATWOOD, University of Wisconsin, Madison
ENGINEERING SOLUTIONS TO EXTEND HUMAN HEALTHSPAN - $50,000
New technologies promise to extend healthspan, but their development is hampered by poor communication between engineers and biologists. To speed technology development, these researchers propose to identify specific healthspan research areas that would benefit from engineer-biologist collaborations.
WOODRING WRIGHT, University of Texas Southwestern Medical Center, Dallas
THE COMPARATIVE CELLULAR BIOLOGY OF AGING - $100,000
Mammalian lifespan varies more than fiftyfold. This researcher will establish a resource of normal and immortalized cultured cells from over 30 species to be shared between laboratories to study the comparative cellular biology of aging. The goal is to identify strategies to manipulate the process of limiting human healthspan.
Source: Maureen O'Leary
The National Academies
John W. Rowe, M.D., professor of health policy and management, Columbia University, New York City, and the conference chair, said, "We received many bold and innovative proposals and believe we have selected the most promising research projects to pursue."
These competitive seed grants aim to fill a critical gap for research on new ideas. Major federal funding programs do not typically provide support in areas that are considered risky or unusual. The FUTURES grants allow researchers to start recruiting students and postdoctoral fellows, purchasing equipment, and acquiring preliminary data - all of which can position the researchers to compete for larger awards from other public and private sources.
Established through a $40 million grant from the W.M. Keck Foundation in 2003, the National Academies Keck FUTURES INITIATIVE is a 15-year effort to enhance communication among researchers, funding agencies, universities, and the general public - with the objective of stimulating interdisciplinary research at the most exciting frontiers. The National Academies and the W.M. Keck Foundation believe considerable scientific progress and social benefit will be achieved by providing a counterbalance to the tendency to isolate research within academic fields. The FUTURES INITIATIVE is designed to enable researchers from different disciplines to focus on new questions and entirely new research, and to encourage better communication among scientists as well as between the scientific community and the public.
The award recipients and their grant research topics are:
STEVEN AUSTAD, University of Texas Health Science Center, San Antonio
DAVID J. WATERS, Purdue University, West Lafayette, Ind.
WORKSHOP ON THE DEVELOPMENT OF DOGS AS ANIMAL MODELS FOR THE STUDY OF EXTENDED HEALTHSPAN - $25,000
These researchers will hold a workshop with experts in basic aging research, canine genomics, epidemiology, pathology, and the assessment of canine health, to develop a research plan to study dogs and breed differences for animal models of extended healthspan.
LAZELLE BENEFIELD, University of Oklahoma Health Sciences Center, Oklahoma City
GEORGE DEMIRIS, University of Washington, Seattle
TAMARA HAYES, JEFFREY KAYE, and MISHA PAVEL, Oregon Health & Science University, Portland
MARGARET PERKINSON, St. Louis University
ELAINE WITTENBERG-LYLES, University of North Texas, Denton
TECHNOLOGY-ENHANCED INTERVENTIONS FOR DISTANCE CAREGIVING OF OLDER ADULTS: AN INTERDISCIPLINARY APPROACH - $50,000
This project will explore information and communication technology solutions to support long-distance caregiving. The researchers will develop the long-term research agenda to assess human-technology interface within an aging-in-place model.
BAMBI BREWER, SUJATA PRADHAN, and ANTHONY DELITTO, University of Pittsburgh
ROBOTIC ASSESSMENT FOR QUANTIFICATION OF PRECLINICAL SYMPTOMS OF NEURODEGENERATIVE DISEASE - $75,000
These researchers will use robotic technology to develop methods to measure early symptoms of degenerative diseases like Parkinson's disease. Such tools could increase the human healthspan by accelerating the development of drug treatment and allowing early diagnosis of these diseases once effective treatment is available.
EILEEN CRIMMINS, University of Southern California, Los Angeles
HUMAN LIFESPAN AND HEALTHSPAN ACROSS TIME AND SPACE - $75,000
This project will estimate the healthspan or life without physiological dysregulation and impaired functioning in a number of populations that span time and space. The information gathered will be used in models that clarify the effects of changing physiological, social, and behavioral characteristics on future healthspan.
DIDDAHALLY GOVINDARAJU, Boston University School of Medicine
STEVE N. AUSTAD, University of Texas Health Science Center, San Antonio
NIR BARZILAI, Albert Einstein College of Medicine, Bronx, New York City
CHARLES LEE, Harvard Medical School, Cambridge, Mass.
COPY NUMBER VARIATION AND EXCEPTIONAL HUMAN HEALTHSPAN: THE ASHKENAZI CENTENARIANS - $87,500
Human genomic length variation ranging from 500bp to 5 Mb, also known as structural or copy number variation (CNV), has been shown to influence complex traits including longevity and diseases. These researchers will investigate this influence by a genome-wide survey of CNVs in relation to longevity among the Ashkenazi centenarians.
CHRISTINE GRANT, North Carolina State University, Raleigh
ANATOLI I YASHIN, KEITH MEADOR, and ELIZABETH ANN GERKEN HOOTEN, Duke University, Durham, N.C.
KHALED SALEH, University of Virginia, Charlottesville
SARA PECKHAM, Wellness Consultant, Cleveland
PARADIGM SHIFT TOWARD POSITIVE HEALTH AND HEALTHSPAN OUTCOMES - $50,000
This project will bring together experts from many fields including orthopedic medicine, biomedicine, and spiritual, wellness, to focus on how orthopedic events will enhance orthopedic medicine and foster health care personnel diversity, facilitating culturally competent care.
SCOTT HOFER, Oregon State University, Corvallis
JEFFREY KAYE, Oregon Health and Science University, Portland
ILENE C. SIEGLER, Duke University, Durham, N.C.
AVRON SPIRO, Boston University
HEALTH AND HEALTHSPAN IN LONGITUDINAL STUDIES OF AGING - $75,000
These researchers will hold a conference to better understand age-related health changes by evaluating measurement and modeling approaches. Using current longitudinal studies of aging, participants will compare the various models, measures, and methods of assessing health and provide an empirical basis for harmonizing existing measures, suggesting novel ones, and eventually integrating health information from new and ongoing longitudinal studies across disciplines.
KENNETH MANTON, Duke University, Durham, N.C.
PLATEAUS IN HUMAN MORTALITY AND DISABILITY DYNAMICS AT ADVANCED AGES - $87,500
This project will examine data from National Long-Term Care Surveys from 1982 to 2004 with data for linked Medicare Part B files for the same dates to see if the age trajectory of human mortality and disability processes reaches a plateau or even declines, above age 95.
MAJA MATARIC and CALEB FINCH, University of Southern California, Los Angeles
SOCIALLY ASSISTIVE ROBOTICS FOR THE PHYSICAL AND COGNITIVE HEALTH - $75,000
Socially assistive robotics (SAR) -- autonomous, intelligent, and companionable technology -- has the potential to positively impact the human healthspan. These researchers will develop and test SAR systems that provide individualized physical and cognitive exercises for improving motivation and function, in a socially engaging context, through social (not physical) human-machine interaction.
RICHARD MILLER, University of Michigan, Ann Arbor
STEVEN AUSTAD, University of Texas, San Antonio
JUDITH CAMPISI, Lawrence Berkeley National Laboratory, Berkeley, Calif.
CALEB FINCH, University of Southern California, Los Angeles
LINDA MILLER, Nature Publishing Group, New York City
CHRISTOPHER K. PATIL, Lawrence Berkeley National Laboratory, Berkeley, Calif.
WOODRING ERIK WRIGHT, University of Texas Southwestern Medical Center, Dallas
COMPARATIVE BIOGERONTOLOGY INITIATIVE - $75,000
These researchers will hold two meetings with senior scholars to develop a plan to test hypotheses about biological factors that control lifespan and healthspan, and compare tissues from multiple species of animals. The scholars are pathologists, comparative physiologists, methodologists, statisticians, and experts in the biology of aging.
STEVEN ORZACK, Fresh Pond Research Institute, Cambridge, Mass.
DIDDAHALLY R. GOVINDARAJU, Boston University School of Medicine
SHRIPAD TULJAPURKAR, Stanford University, Stanford, Calif.
TIM COULSON, Imperial College, London
SIGNATURES OF HEALTHSPAN IN HUMANS - $75,000
These researchers will study the causal basis for differences in human healthspan by using "signatures" and health trajectories, and assessing the dynamic nature of heterogeneity of healthspan.
CORINNA ROSS, University of Texas Health Science Center, San Antonio
SARA ESPINOZA, University of Texas, San Antonio
DEVELOPMENT OF A SMALL PRIMATE MODEL OF FRAILTY - $25,000
Frailty has been defined as a wasting syndrome characterized by weight loss, fatigue, weakness, and vulnerability to stressors that predisposes them to increased risk of morbidity and mortality. These researchers will convene a group of experts to explore the development of a small primate model of frailty.
RICHARD SPROTT, The Ellison Medical Foundation, Bethesda, Md.
CREATING A CENTER FOR MODELS FOR HEALTHSPAN RESEARCH - $75,000
There are currently no accepted models for healthspan research. A universally accessible center for model development and maintenance would make an enormous contribution to this essential research. This project is to convene a group of experts to develop guidelines for healthspan models.
CATHERINE WOLKOW, National Institute on Aging Intramural Research Program, Bethesda, Md.
NAN JOKERST, Duke University, Durham, N.C.
CRAIG S. ATWOOD, University of Wisconsin, Madison
ENGINEERING SOLUTIONS TO EXTEND HUMAN HEALTHSPAN - $50,000
New technologies promise to extend healthspan, but their development is hampered by poor communication between engineers and biologists. To speed technology development, these researchers propose to identify specific healthspan research areas that would benefit from engineer-biologist collaborations.
WOODRING WRIGHT, University of Texas Southwestern Medical Center, Dallas
THE COMPARATIVE CELLULAR BIOLOGY OF AGING - $100,000
Mammalian lifespan varies more than fiftyfold. This researcher will establish a resource of normal and immortalized cultured cells from over 30 species to be shared between laboratories to study the comparative cellular biology of aging. The goal is to identify strategies to manipulate the process of limiting human healthspan.
Source: Maureen O'Leary
The National Academies
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