National Institutes of Health Awards Rutgers $47.5 Million to Advance Groundbreaking Research on Protein Structures

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

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.

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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

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

“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

“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
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