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National Institutes of Health Awards Rutgers $47.5 Million to Advance Groundbreaking Research on Protein Structures
Two grants are part of national research effort to advance knowledge of protein interactions that cause or promote diseases
NEW BRUNSWICK, N.J. – The National Institutes of Health (NIH) has awarded Rutgers University $47.5 million to advance groundbreaking research on three-dimensional protein structures and to collect and disseminate protein structure information among scientists worldwide. The work helps scientists understand protein interactions that cause or promote diseases and helps scientists devise therapies to combat these diseases.
The Rutgers grants are among 23 that the NIH has awarded this past month for structural biology research, totaling up to $290 million over five years. The awards are the next step in the funding agency’s Protein Structure Initiative (PSI), an effort begun in 2000 to develop highly efficient ways to reveal the three-dimensional (3D) structures of many different proteins.
Rutgers manages two major programs as members of the PSI. One is the Northeast Structural Genomics Consortium (NESG), and second is the Structural Biology Knowledgebase (previously called the Structural Genomics Knowledgebase). The former is receiving $35 million; the latter, $12.5 million.
Over the past decade, NESG has developed new methods and tools to streamline the laborious steps involved in determining 3D protein structures – the complex series of twists and shapes of protein molecules. These shapes influence how proteins regulate life functions and promote or prevent disease. NESG is a consortium of nine universities and research facilities led by Gaetano Montelione, professor of molecular biology and biochemistry at Rutgers. Montelione was recently appointed as the university’s first holder of the Jerome and Lorraine Aresty Chair in Cancer Research.
Montelione and his colleagues use nuclear magnetic resonance (NMR), X-ray crystallography and computational methods to determine these structures. In addition to activities at Rutgers, NESG integrates activities at Columbia University, University of Buffalo, University of Toronto and several other academic institutions. Over the past 10 years of the PSI program, the group has determined nearly a thousand 3D protein structures using techniques that investigators have developed.
“The PSI program, a follow-on to the human genome sequencing project, has contributed extensive new information about the structures and functions of tens of thousands of proteins,” Montelione said. He noted that NESG has made essential contributions by determining 3D structures of proteins associated with cancer, developmental biology, viruses and their complexes with human host proteins, and bacterial pathogens, such as those that infect immuno-compromised AIDS patients.
“These structures provide new insights into how these protein molecules work and point to new targets for therapeutic drug development,” he said.
The Structural Biology Knowledgebase (SBKB) collects and disseminates data generated by investigators in the PSI network, including protein structures, theoretical models, protocols and technologies. The SBKB also provides central access to genetic, structural and functional annotations from more than 150 publicly available biological databases, and to the protein structures in the Protein Data Bank (PDB), an online resource of experimentally determined biological structures. Both the SBKB and the PDB are maintained by the Research Collaboratory for Structural Biology, directed by Helen M. Berman, Board of Governors Professor of Chemistry and Chemical Biology at Rutgers.
"The SBKB has been designed to give facile access to information about every step in the protein structure determination pipeline as well as the roles of these proteins in living systems and disease,” Berman said. “Over the coming years, we will continue to expand the scope of our services so as to better enable biological research.”
Montelione and Berman are also resident members of the Center for Advanced Biotechnology and Medicine (CABM), a research and teaching institute jointly administered by Rutgers and the University of Medicine and Dentistry of New Jersey. Both are also faculty in the Rutgers School of Arts and Sciences.
NIH funding for the third phase of the PSI, known as PSI:Biology, is through the agency’s National Institute of General Medical Sciences (NIGMS), which supports basic research to increase understanding of life processes and lay the foundation for advances in disease diagnosis, treatment and prevention. The PSI:Biology phase will use methods developed during the PSI’s first decade to generate protein structures that can help guide functional studies by laboratories around the world. For example, in addition to its primary focus on networks of human proteins associated with cancer biology, the NESG consortium will collaborate with groups around the country to determine structures of proteins involved in various aspects of cell biology, such as gene regulation, metabolism, and the engineering of novel proteins.
“Another key goal of the initiative is to make the resources generated by the PSI available to the broader scientific community,” said Ward Smith, director of the PSI: Biology program. “These Rutgers efforts are key to achieving this goal – the NESG will partner with biologists to solve functional studies while the SBKB will put all the PSI’s results at one’s fingertips.”
Media Contact: Carl Blesch