This one-year grant constitutes the third year of funding for a five-year, $27 million pilot project. Its purpose is to develop technologies required for determining the three-dimensional structure of the wealth of protein molecules whose coding was revealed through the Human Genome Project.
NIH initially funded the five-year project on a year-by-year basis but, based on progress to date, NIH has assured the project's funding for the full five years. NIH has even added a $1.5 million supplement to this year's funding for new robotic equipment that will eliminate a serious process bottleneck in protein sample production.
"Charting these molecular structures will lead us to a clearer understanding of how proteins work and will provide opportunities for the development of new drugs to treat human diseases," said Joseph J. Seneca, university vice president for academic affairs. "Rutgers' leadership role in this major scientific research project affirms the extraordinary expertise and accomplishments of our faculty."
"The completion of the Human Genome Project was not the end of something – it was just the beginning, and this is the next big step," said Gaetano Montelione, a resident faculty member of the Center for Advanced Biotechnology and Medicine (CABM) and the principal investigator in the consortium. "Rutgers is the core for one of nine NIH-funded pilot projects in large-scale structural genomics, which have the potential to revolutionize the value and impact of structural biology."
"This outstanding program is very important to the continued growth and development of the center and the life sciences in general on our campus," said Aaron Shatkin, director of CABM, which is jointly sponsored by Rutgers, The State University of New Jersey, and the University of Medicine and Dentistry of New Jersey (UMDNJ).
Montelione explained that genes provide the blueprint for the assembly of proteins – the machines that carry out the biological processes of life. Using the blueprints derived through the Human Genome Project, scientists now know of tens of thousands of new proteins that no one had ever seen or even knew existed. "Now the questions are what do these proteins do, what do they look like and how do they work," said Montelione, who is also a professor of molecular biology and biochemistry at Rutgers and professor of biochemistry at the Robert Wood Johnson Medical School of UMDNJ.
The NIH-funded NESG project has two goals: to make protein structure determination less expensive and to determine the 3-D structures of hundreds of new proteins. By streamlining methodologies and developing new ones, the consortium expects to reduce the cost per structure from about $300,000 to $10,000 or $20,000. The primary techniques currently used are X-ray crystallography and nuclear magnetic resonance spectroscopy (NMR), both of which provide 3-D representations of protein structures. The development of NMR for analyzing protein structure brought a 2002 Nobel Prize in chemistry to Swiss chemist Kurt Wuethrich and two colleagues. Wuethrich was an adviser in Montelione's doctoral studies.
The Rutgers campus is a hub for biomolecular NMR. Montelione and his colleagues have even developed and introduced specialized software to automate NMR data analysis – a prime example of the streamlining effort. They are also working on an NMR fund-raising initiative to acquire additional NMR machines, whose costs range from $1 million to $2.5 million each.
The huge number of proteins derived from the Human Genome Project necessitates grouping similar proteins into families and then determining the structure of representative family members. Consortium researchers have now identified 30,000 protein families with about 100 members in each. Five thousand of these proteins have been targeted as candidates for structural determination by the NESG research network with the aim of determining 3-D structures of a few hundred proteins over the next three years.
The NESG Consortium is a research network made up of scientists from Rutgers, UMDNJ, Columbia University, Cornell University, Hauptman Woodward Research Institute (Buffalo), Pacific Northwest National Laboratories (Washington state), the State University of New York – Buffalo, the University of Toronto and Yale University. Approximately one-half of the project's NIH funding will support activities at Rutgers and UMDNJ. The balance of the funding is distributed across the NESG research network.
This project is an extension of earlier activities set in motion by funding from a Research Excellence Award through the New Jersey Commission on Science and Technology Initiative in Structural Genomics and Bioinformatics, provided to Montelione and colleagues at CABM.
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