The National Institute of General Medical Sciences (NIGMS) has awarded Albert Einstein College of Medicine of Yeshiva University a five-year, $30 million grant to study the structure and function of thousands of biomedically important proteins.
"Determining the structures of proteins is the first step toward understanding their role in normal biological processes as well as in disease pathways," says principal investigator Steven Almo, Ph.D., professor of biochemistry and of physiology & biophysics at Einstein. "Using this knowledge, we can begin to learn how proteins can be modified to create new, highly targeted therapies for disease."
Proteins are key building blocks of all living things. They are involved in all normal bodily processes including movement, metabolism and cognition. They also play central roles in a wide range of illnesses, including autoimmune diseases, infectious diseases and cancer.
The Einstein research is part of the NIGMS's Protein Structure Initiative (PSI), a decade-long federal, university and industry effort aimed at dramatically reducing the costs and lessening the time it takes to determine a three-dimensional protein structure from its DNA sequence.
"The PSI has been incredibly successful in establishing high-throughput pipelines that have led to more than 5,000 structures, most unlike any we've seen before," says Jeremy Berg, Ph.D., director of NIGMS, a division of the National Institutes Health (NIH). "Now it's time to deploy these capabilities so we can advance our understanding of the role proteins play in health and disease."
PSI is entering its third five-year phase, called PSI:Biology, which will support four large-scale centers that will operate pipelines for determining protein structures nominated by the scientific community or identified by collaborating biologists. Among these centers is the New York Structural Genomics Research Consortium (NYSGRC), which is based at Einstein and has been part of PSI since its inception.
Under Einstein's leadership, NYSGRC will initially work with two PSI partnership centers to concentrate on particular areas of biological interest. One of NYSGRC's partners is the Immune Function Network (IFN), a consortium of immunologists, geneticists, computational biochemists and high-throughput structural biologists led by Stanley Nathenson, M.D., Samuel H. Golding Chair in Microbiology, and distinguished professor of microbiology & immunology and of cell biology at Einstein, as well as Almo. Together, NYSGRC and IFN will study cell surface molecules that control the immune response, as well as substances that major bacterial, protozoan and fungal pathogens secrete to evade the immune system or to modulate host signaling pathways. "We hope that the synergy between the IFN and the NYSGRC will lead to the development of new strategies and new molecules that are useful in the clinic," says Dr. Almo, who is also scientific director of Einstein's macromolecular therapeutics development facility, where much of the research will take place.
The second partnership, with Stanford University and the Sanford-Burnham Medical Research Institute, will focus on proteins involved in cell adhesion, the process by which cells recognize and bind to other cells and structures in the body. It is anticipated that additional PSI partnership centers will join NYSGRC in the future.
In another project NYSGRC will study proteins found in so-called Category A, B and C "Priority Pathogens" (such as anthrax and botulism) - microbes designated by the NIH and the Centers for Disease Control and Prevention (CDC) as the most relevant pathogens for biodefense and emerging disease studies. Here, NYSGRC will work in conjunction with the Northeast Biodefense Center (NBC), one of eleven federally-funded regional centers for biodefense and emerging infectious disease research, with the goal of developing new vaccines and treatments. "We are delighted that our members have access to this extraordinary resource" said W. Ian Lipkin, M.D., director of the NBC.
Other investigators in the NYSGRC include Andras Fiser, Ph.D., Mark Girvin, Ph.D., Ronald Seidel, Ph.D., and Jeff Bonanno, Ph.D. at Einstein; Subramanyam Swaminathan, Ph.D., of Brookhaven National Laboratory; Andrej Sali, Ph.D., of the University of California, San Francisco; David Baker, Ph.D., of the University of Washington; and Wladek Minor, Ph.D., of the University of Virginia.
Earlier this year, a team that includes Drs. Almo, Bonanno and Seidel received a prestigious NIH "Glue Grant" to develop a strategy for discovering the structure and function of unknown enzymes identified in genome-sequencing projects. Glue Grants, which are also issued by the NIGMS, provide resources to tackle complex problems that are of central importance to biomedical science and beyond the means of any one research group. The research will improve understanding of the metabolic and chemical diversity that exists in nature and may result in new drug targets for treatments. It may also lead to new enzymes that could prove useful for catalyzing industrial processes. Over the next five years, the Glue Grant will provide $33.9 million in funding, of which Einstein will receive approximately $11 million.
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