University News
Two NIH Initiatives Launch Intensive Efforts to Determine Genetic and Environmental Roots of Common Diseases
Representatives of The Department of Health and Human Services (HHS) announced the creation of two new, closely related initiatives to speed up research on the causes of common diseases such as asthma, arthritis and Alzheimer’s disease.
One initiative boosts funding at the National Institutes of Health (NIH) for a multi-institute effort to identify the genetic and environmental underpinnings of common illnesses. The other initiative launches a public-private partnership between NIH, the Foundation for the National Institutes of Health (FNIH) and major pharmaceutical and biotechnology companies, especially Pfizer Global Research & Development of New London, Conn.; and Affymetrix Inc. of Santa Clara, Calif., to accelerate genome association studies to find the genetic roots of widespread sicknesses. The genetic analysis component of the two initiatives is highly complementary.
Genes and Environment Initiative
HHS Secretary Mike Leavitt announced on Monday that the President’s budget proposal for fiscal year (FY) 2007 includes US$68 million for the Genes and Environment Initiative (GEI), a research effort at NIH to combine a type of genetic analysis and environmental technology development to understand the causes of common diseases. The FY 2007 budget represents a $40 million increase above the $28 million already planned for these efforts in the NIH budget.
If approved by Congress, this additional federal funding will begin in FY 2007 and continue for multiple years. Of the first year’s funding, $26 million will go to genetic analysis and $14 million for the development of new tools to measure environmental exposures that affect health.
GEI will have two main components: a laboratory procedure for efficiently analyzing genetic variation in groups of patients with specific illnesses and a technology development program to devise new ways of monitoring personal environmental exposures that interact with genetic variations and result in human diseases.
The proposed federal funding level will enable GEI to perform genetic analysis — or genotyping — studies for several dozen common diseases. The exact diseases to be studied will be determined by peer review. An initial survey of existing NIH-supported clinical studies identified more than 100 with sufficient numbers of already characterized patients to get this effort started. In addition, NIH expects to develop four new environmental monitoring devices a year.
Public-Private Partnership
At the same time, a public-private partnership between NIH, FNIH, which is a non-profit foundation established by Congress to support the mission of the NIH; Pfizer and Affymetrix is being created to further accelerate this important research on the genetic association studies.
The new partnership, called the Genetic Association Information Network (GAIN), is being launched with a $5 million donation from Pfizer to set up the management structure and $15 million worth of laboratory studies to determine the genetic contributions to five common diseases. Affymetrix, a biotech company that develops the types of tools used in these kinds of genetic studies, will contribute enough laboratory resources to study two additional common diseases. On average, it costs about $3 million to carry out one study.
GAIN will be an FNIH-managed partnership that includes NIH, industry, foundations, individuals and advocacy groups. Governance will include an executive committee, a steering committee, as well as peer review and data access committees.
Genetic Factors
The genetic analysis of both GAIN and GEI will focus on the alternative spellings — called single nucleotide polymorphisms or SNPs — that normally occur in the order of the 3 billion DNA base pairs or letters that make up a person’s genome. SNPs are like single-letter misspellings of a word. Most of these genetic variations are biologically meaningless. But a small fraction of these SNPs alter the function of a gene — often only slightly. The combination of many slightly altered genes may significantly increase the risk of a specific disease, but identifying such a complex set of genetics changes is challenging. Finding these disease-causing variants is one of the highest priorities of current biomedical research.
There are about 10 million common SNPs in the human population. Scanning the genomes of large numbers of patients for such a large number of variants would be prohibitively expensive. Fortunately, a major shortcut has been discovered that reduces the workload about 30-fold. The International HapMap Project, led by the NIH and completed in October 2005, demonstrated that the 10 million variants cluster into local neighborhoods, called haplotypes, and that they can be accurately sampled by as few as 300,000 carefully chosen SNPs. New technological systems allow these SNPs to be systematically studied in high-throughput facilities that dramatically lower the cost.
For each study of 1,000 to 2,000 patients with a specific disease and a similar number of people who do not have the illnesses (controls), an investment of $3 million to $6 million (depending on the number of patients and controls) is needed for the first stage of genotyping. Follow-up studies to validate the results with additional patients and controls, data analysis, and patient management expenses will add to these basic costs. It is important to note, however, that these costs are a small fraction of what has already been invested in enrolling these study subjects, examining them, carrying out extensive laboratory investigations, and collecting their DNA.
The genotyping work itself will be performed by either commercial or government laboratories. The initial GAIN genotyping supported by Pfizer will be carried out by Perlegen Sciences, Inc., of Mountain View, Calif., and will start in late summer 2006; Pfizer is contributing these Perlegen-produced genotypes as an “in kind” donation to the project. A similar arrangement will be worked out with Affymetrix. Federally funded genotyping for GEI will be managed by an NIH coordinating committee under the usual government rules, subject to competition between research facilities, and begin in FY 2007.
The research will lead directly to the identification of major genetic susceptibility factors for common diseases of substantial public health impact — disorders such as heart disease, diabetes, cancer, stroke, Alzheimer’s disease, schizophrenia, osteoporosis, asthma, cataracts, hypertension, Parkinson’s disease, autism and obesity. The target diseases and the populations studied have yet to be selected and will be subject to a peer-review process.
Environmental Factors
Genes alone do not tell the whole story. Recent increases in chronic diseases like diabetes, childhood asthma, obesity or autism cannot be due to major shifts in the human gene pool. They must be due to changes in the environment, including diet and physical activity, which may produce disease in genetically predisposed persons. Therefore, GEI will also invest in innovative new technologies to measure environmental toxins, dietary intake and physical activity, and to determine an individual’s biological response to those influences, using new tools of genomics, proteomics and metabolomics.
To determine how the environment, diet and physical activity contribute to illness, investments will be made in emerging technologies, such as small, wearable sensors that can measure environmental agents that have contact with the body and individual measures of activity. Devices also will be developed that measure changes in human biology, which can be observed in samples of blood or urine. In aggregate, these new tests will provide the precision needed to help determine how these factors influence the genetic risk of developing disease. The goal is to produce devices for application to eventual population studies, to speed up data processing, to enhance accuracy and to reduce cost.
With the $14 million annual investment in the environmental component of this initiative, NIH will develop technologically advanced measures of dietary intake, precise personalized measures of physical activity, and biological measures that identify prior exposures to potential toxins such as metals and solvents. NIH also will assess disease indicators like inflammation and oxidative stress that are known to be influenced by environmental toxins.
The National Center for Biotechnology Information, a part of the National Library of Medicine at NIH, will develop databases to manage the vast amount of genetic, medical and environmental information that will emerge from these initiatives. To encourage rapid research advances, and in keeping with the principles pioneered by the Human Genome Project and increasingly common in such pre-competitive public/private partnerships, all data generated through these initiatives will be placed in the public domain.
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Annenberg School for Communication Receives $10 Million for Global Communication from Annenberg Foundation
The Annenberg School for Communication at the University of Pennsylvania will receive a US$10 million endowment from the Annenberg Foundation of St. Davids, Pa. The funding is in support of The Project for Global Communication Studies, which was established in 2004 at the Annenberg School, to expand and coordinate its work in international, global and comparative communication research and studies.
The Project for Global Communication Studies conducts and facilitates research; coordinates faculty and student exchanges; organizes conferences; provides consulting and advisory assistance to academic, non-profit and governmental institutions; and builds formal and informal networks among individuals and organizations working in global communication. Particular emphasis is placed on understanding the role of new information technologies and communication policies and practices in emerging and established democracies. PGCS also offers research and internship opportunities in cities across the world, including Beijing, Budapest, London, Oxford and Moscow.
The Annenberg Foundation is a private foundation established in 1989. It exists to advance the public well-being through improved communication. As the principal means of achieving its goal, the Foundation encourages the development of more effective ways to share ideas and knowledge.
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UTD Center Receives Three Grants for Brain Research Totaling More Than $500K
The Center for BrainHealth® at The University of Texas at Dallas (UTD) has received three separate grants totaling more than US$500,000 for brain health research initiatives ranging from improving decision–making skills and functioning to how kidney disease affects the brain to helping children achieve academic and social success following a brain injury.
The first gift, a $400,000 commitment from Dallas philanthropists John and Lee Wacker, will help launch the “Healthy Brain Initiative for Young Adults.” The program will focus on research and intervention for impaired social cognition, which affects the ability to make decisions, assume responsibility and get along with others. Impaired social cognition has been linked to dysfunction of the frontal and temporal brain regions. By intervening with young adults, the center hopes to reach them during a critical stage in their social development.
The new initiative meshes with the Wackers’ interests — the couple has long been fascinated by neurological explanations for behavioral problems that historically were attributed to psychological dysfunction.
The second award, a $60,000 grant from Kidney Texas, Inc., will allow researchers at the center to further examine the effects of kidney disease on brain function in children.
Previous studies have found that renal failure has a detrimental impact on youths’ cognitive development. With the grant, UTD researchers plan to develop a clinical and research program called “Kidney–Brain Connection,” which is specifically designed to study the long–term effect of speech/language and cognitive treatment services for children. The scientists hope to develop a format for following and maximizing the potential of children who suffer from the disease and make rehabilitation services available to help them succeed in home, school and community environments.
The third gift, a $60,000 award from an anonymous donor, will allow researchers at the center to create a national program to define pediatric care in the presence of brain disease or injury. Traumatic brain injury is the leading cause of acquired disability in children, but there currently are no research–based therapeutic models for helping children develop skills for academic and social success post–injury.
The gift will allow for a controlled, randomized study that will compare current standards of care to the center’s program of targeted intervention to develop strategic learning skills. Researchers hope that, if successful, the center’s model program could be replicated across the country, eventually creating a permanent change in the lives of children living with brain injuries.
The center’s director, Dr. Sandra Bond Chapman, who also holds the Dee Wyly Distinguished Chair for Brain Health, said she hopes the gifts and grant will help to dramatically and positively change the lives of adults and children touched by brain injury or disease.
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Cummings Elected American Physical Society Fellow
Peter T. Cummings -- John R. Hall Professor of Chemical Engineering at Vanderbilt University and director of the Nanomaterials Theory Institute of the Center for Nanophase Materials Sciences at the Department of Energy’s Oak Ridge National Laboratory – has been elected a fellow of the American Physical Society.
Cummings was elected for “contributions to our molecular understanding of industrially relevant fluids and processes, and for national leadership in applied molecular modeling and computational nanoscience,” according to a letter from the society informing him of his election.
His research focuses on computer-based modeling of chemical, biological and materials systems, with particular recent emphasis on nanoscience and nanotechnology applications of such systems.
Cummings has authored more than 270 refereed journal papers on these topics that have appeared is such publications as the Journal of American Physics, the Journal of Chemical Physics and Physical Review Letters. He is a frequently invited speaker at international meetings throughout the world.
He edits the publication Fluid Phase Equilibria, one of the world’s prominent engineering thermodynamics journals, and has frequently served at the national level on advisory committees planning future research focuses for federal funding of research.
Cummings earned a bachelor’s degree in 1976 with first class honors in mathematics from the University of New Castle in Australia before earning a doctorate in 1980 in applied mathematics from Australia’s Melbourne University. He has been associated with ORNL since 1994.
ORNL is managed by UT-Battelle for the Department of Energy.
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UGA Senior Vice President Huckaby to Retire
Henry M. (Hank) Huckaby, the University of Georgia’s senior vice president for finance and administration, has announced that he will retire June 30, concluding nearly 40 years of public service to the state of Georgia.
Huckaby assumed his post as the university’s chief financial officer in 2000 after serving three years as director of UGA’s Carl Vinson Institute of Government. Previously he worked 22 years in state government including five years as the state’s top budgeting and finance officer.
The senior vice president for finance and administration oversees all business operations at the university including the departments for budget, accounting services, banking and investments and human resources. The senior vice president is also responsible for the physical plant, auxiliary and administrative services, facility planning and environmental safety.
UGA President Michael F. Adams said a search committee will be appointed and a national search conducted for a successor to Huckaby with the goal of having the new person in place by July 1.
Before joining UGA, Huckaby was director of the Office of Planning and Budget, the highest financial position in state government, under Gov. Zell Miller. He also served as executive director of the Georgia Housing and Finance Authority under Gov. Joe Frank Harris, and as the commissioner of the Georgia Department of Community Affairs under Gov. George Busbee.
In November 2002, Gov.-elect Sonny Perdue appointed Huckaby to his transition team and subsequently as interim chief financial officer. He served in this dual role for eight months before returning full-time to his duties at UGA.
Huckaby said implementing technological advances to improve administrative operations at UGA is a major accomplishment of his tenure as senior vice president.
Another source of pride is progress in implementing the Campus Master Plan, including the opening of the Student Learning Center, the expansion of Sanford Stadium, the renovation and modernization of older facilities, and the partnership with UGA’s Real Estate Foundation to construct several major new buildings and strategically acquire property to extend campus borders. East Campus Village, the Complex Carbohydrate Research Center and the Coverdell Center for Biomedical and Health Sciences are among new facilities completed through UGA’s partnership with the Real Estate Foundation.
A strategic plan has been put into place for the finance and administration division that calls for greater diversity in staffing, additional resources for staff and more opportunities for staff development and professional growth.
Last November Huckaby received a national career achievement award from the Association for Budgeting and Financial Management. The award--one of the highest in the field of public budgeting and finance--recognized Huckaby for “exemplary work and professional integrity” in advancing the profession of public financial management.
Huckaby received a bachelor’s degree in political science and a master’s degree in business administration from Georgia State University and began his public service career there, serving from 1967-1971 as assistant dean of admissions.
He was a senior policy planner in the Office of Planning and Budget and the first director of the Georgia State Senate Research Office before becoming community affairs commissioner in 1977.
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With a New Method Scientists Can Identify Novel Protein Molecules in Days Rather than Months
A team of scientists at the Weizmann Institute of Science and the Hebrew University of Jerusalem has developed a method that could speed up the process of identifying novel protein molecules for medical or biological research hundreds of times over.
In today’s high-throughput searches for specific genes, proteins or protein interactions, plates containing rows of tiny wells have replaced old-fashioned test tubes. However, trawling for a gene or protein with just the right qualifications may require sorting through millions, or even billions, of possibilities. Instead of wells, the new method, developed by Dr. Dan Tawfik and Amir Aharoni of the Institute’s Biological Chemistry Department and Prof. Shlomo Magdassi of the Hebrew University’s Institute of Chemistry with support from the Israel Ministry of Science and Technology, relies on microscopic droplets of water suspended inside oil droplets. Using their system, millions of tests can be performed at once.
The method, which relies on a type of emulsion dubbed WOW, for water-oil-water, takes a page from living cells, which employ a fatty membrane to keep the inside and outside environments separate. The oily layer surrounding each miniscule water droplet acts as a barrier, keeping genes, proteins and other materials contained. Alternately, the team inserted harmless bacteria containing genes for testing into the drops. Confining individual tests within a cell-like bubble allowed them to employ a widely-used method for analyzing living cells. This method involves adding a fluorescent marker that lights up in color when activated by the right protein and sorting through the cells for those containing the marked proteins and their coding genes. Automated devices for sorting cells can handle many thousands of droplets per second.
To demonstrate the efficiency of the system, the team isolated a new enzyme from a gene that was mutated artificially to produce random variations. They generated the enzymes in the droplets and sorted them according to which ones were better at cleaving a specific toxin in the bloodstream. The results from a screen completed in one afternoon were equivalent to those previously obtained through several rounds of mutation and screening – a several-month process.
Dr. Dan Tawifik’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the Dolfi and Lola Ebner Center for Biomedical Research; the Estelle Funk Foundation; the Dr. Ernst Nathan Fund for Biomedical Research; the Henry S. and Anne Reich Family Foundation; the Charles and M.R. Shapiro Foundation Endowed Biomedical Research Fund; the Harry and Jeanette Weinberg Fund for Molecular Genetics of Cancer; the Eugene and Delores Zemsky Charitable Foundation Inc; and Mr. and Mrs. Mordechai and Dalia Segal, Israel. Dr. Tawfik is the incumbent of the Elaine Blond Career Development Chair.
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New Planet Hunting Technique Pays Off
Using a relatively new planet-hunting technique that can spot worlds one-tenth the mass of our own, researchers have discovered a potentially rocky, icy body that may be the smallest planet yet found orbiting a star outside our solar system.
The discovery suggests the technique, gravitational microlensing, may be an exceptional technology for finding distant planets with traits that could support life.
"This is an important breakthrough in the quest to answer the question 'Are we alone?'" said Michael Turner, assistant director for the National Science Foundation (NSF) mathematical and physical sciences directorate. "The team has discovered the most Earth-like planet yet, and more importantly, has demonstrated the power of a new technique that is sensitive to detecting habitable planets. It can probe a much greater portion of our galaxy and is complementary to other techniques."
Located more than 20,000 light years away in the constellation Scorpio, close to the center of our Milky Way galaxy, planet OGLE-2005-BLG-390Lb is approximately five-and-a-half times the mass of Earth.
Orbiting a star one-fifth the mass of the sun at a distance almost three times that of Earth's orbit, the newly discovered planet is frigid: the estimated surface temperature is -364 degrees Fahrenheit (-220 degrees Celsius).
Although astronomers doubt this cold body could sustain organisms, researchers believe gravitational microlensing will bring opportunities for observing other rocky planets in the "habitable zones" of stars - regions where temperatures are perfect for maintaining liquid water and spawning life.
The discovery, authored by 73 collaborators from 32 institutions, appears in the Jan. 26 issue of the journal Nature .
OGLE (Optical Gravitational Lensing Experiment) project telescopes first observed the lensing event on July 11, 2005. In an attempt to catch microlensing events as they occur, OGLE scans most of the central Milky Way each night, discovering more than 500 microlensing events per year. But to detect the signature of low-mass planets, astronomers must observe these events much more frequently than OGLE's one survey per night.
So, when OGLE detected the July 11 lensing, its early warning system alerted fellow astronomers across the globe to microlensing event OGLE-2005-BLG-390 (for the 390th galactic bulge OGLE discovered in 2005). At that point, though, no one knew a planet would emerge.
"The only way to realize the full scientific benefit of our observations is to share the data with our competition," said co-author Bohdan Paczynski of Princeton University, who along with Andrzej Udalski of Warsaw University Observatory and their colleagues co-founded OGLE in 1997.
The telescopes of PLANET (Probing Lensing Anomalies NETwork) and RoboNet tracked the July 11 episode to completion, providing the data that confirmed the presence of a previously unknown planet. These telescopes collect observations more frequently in an attempt to detect the microlensing signature of planets.
"This discovery was possible because the sun never rises on the PLANET collaboration," said lead author and PLANET researcher Jean-Philippe Beaulieu of the Institut d'Astrophysique de Paris, France. "The global nature of the PLANET collaboration was crucial for obtaining data throughout the 24-hour planetary signal," he added.
Ironically, when preparing the final report, the researchers discovered that during its test runs, the new MOA (Microlensing Observations in Astrophysics) telescope, MOA-2, had taken additional measurements of the lensing event. The 6-foot (1.8-meter) aperture telescope has a wider field-of-view than the OGLE telescope, enabling it to observe 100 million stars many times per night. MOA-2 is one of several recent and future advancements that gravitational microlensing proponents hope will greatly increase the number of Earth-like planet discoveries.
OGLE also has plans to increase the field-of-view of its own telescope, and other microlensing groups are proposing to build a new telescope in South Africa. They have also proposed a space mission to see planets as small as Mars as well as free-floating planets that no longer orbit a host star.
"The new discovery provides a strong hint that low-mass planets may be much more common than Jupiters," said co-author and PLANET researcher David Bennett of the University of Notre Dame. Most extrasolar planets found so far have been Jupiter-sized.
"Microlensing should have discovered dozens of Jupiters by now if they were as common as these five-Earth-mass planets. This illustrates the primary strength of the gravitational microlensing method: its ability to find planets of low-mass," Bennett said.
Low-mass planets can yield signals that are too weak to detect with other methods. With microlensing, the signals of low-mass planets are rare but not weak. Thus, the rate of low-mass planet discoveries should increase dramatically if more microlensing events can be searched for planetary signals.
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Scientists Discover Oldest-Known and Most-Primitive Tyrannosaur
Scientists have discovered a new genus and species of dinosaur, which is also the oldest-known and most-primitive tyrannosaur. Guanlong wucaii , the newly discovered dinosaur, was much smaller, however, than its gigantic and legendary relative--the 15-foot tall, 40-foot long Tyrannosaurus rex .
Guanlong wucaii is a small theropod dinosaur called a coelurosaur, like T. rex , which is most closely related to birds.
According to a report in this week's issue of the journal Nature , several of the skeleton's cranial features and long and shallow snout differs from other tyrannosaurs. Still, Guanlong is identified as a tyrannosaur based on the shape of its teeth, the shape of openings in its skull, and its pelvic features, said James Clark of George Washington University in Washington, D.C.
Clark led the scientific team, along with paleontologist Xu Xing of the Institute of Vertebrate Paleontology and Paleoanthropology in Beijing, China. The animal's forelimbs are relatively large compared to its hind limbs and slightly bowed, similar to other coelurosaurs, the scientists say.
In Chinese, the word guanlong means "crested dinosaur." Wucai refers to the rich colors of the rocks where the specimens were found. The dinosaur was unearthed in the Junggar Basin of Xinjiang (pronounced shin jang), China, near the Gobi Desert. Dinosaur beds there lie in the Middle to Late Jurassic Shishugou Formation, one of the few fossil deposits preserving dinosaurs from the time when they had begun to reach enormous sizes and dominate the world's terrestrial ecosystems.
The discovery is "a breakthrough in going deep in time to trace the evolution of coelurosaurs, a process culminating in the origin of birds," said Xing.
Guanlong's most striking feature is a large, complex, fragile cranial crest that runs from its nose to the back of its head. Guanlong is the only species of tyrannosaur known to have this crest. Scientists are unsure of the function of the exaggerated ornament, but suggest it may be useful in display or species recognition.
The team found two specimens of Guanlong wucaii with five different carnivorous dinosaurs in an apparent mud pit.
One of the two new specimens, which died at age 12, is a mostly preserved skeleton. The other specimen, which died at six, is smaller but nearly complete. Guanlong likely reached adult size at seven. The two specimens date back to the Upper Jurassic, approximately 150 million years ago.
John Francis, vice president for research, conservation and exploration at the National Geographic Society (NGS), which also supported the research, said the society "is thrilled to have played a part in the discovery of this important new tyrannosaur. This fossil adds significant new knowledge about a little-known prehistoric period."
Other team members include Catherine Forster of the State University of New York at Stony Brook, Mark Norell of the American Museum of Natural History, Gregory Erickson of Florida State University, David Eberth of the Royal Tyrrell Museum, and Chengkai Jia and Qi Zhao of IVPP.
In addition to NSF and NGS, the research was supported by the National Natural Science Foundation of China, Jurassic Foundation, Hilmar Tharp Sallee Charitable Trust, George Washington University, Chinese Academy of Sciences and American Museum of Natural History.
