In order for John Bushweller and his colleagues at the University of Virginia to do their work in biopolymers, they’ve often found themselves having to pack up their belongings and haul them to as far away as Wisconsin.
Without the proper equipment at their own school to get the necessary data, Bushweller and his seven colleagues have had to use facilities elsewhere. But armed with a $2 million federal grant, continuing their research into membrane proteins soon won’t be a frequent-flier endeavor.
Bushweller’s grant was one of 14 recently announced by the National Institutes of Health’s National Center for Research Resources. The grants, totaling $21.5 million, are aimed at helping institutions purchase expensive equipment. They are administered under the NCRR’s High-End Instrumentation Grant Program.
“It’s really critical to research infrastructure that this continues to provide these kinds of resources.
Among the three hospitals and 11 universities that received the grants, three, including UVa, will use the money to buy instruments to help them study proteomes or proteins.
Bushweller’s group will use its grant to purchase an 800-megahertz nuclear magnetic resonance spectrometer, and the University of California, Santa Barbara will use its $2 million grant to buy an NMR spectrometer to help it study protein interactions with bacteria.
The University of Washington will use the $500,000 it was awarded to purchase a multi-tiered proteomic compute cluster for a protein chemistry study of lung injury diseases, toxicity, and drug-induced liver disease.
According to Bushweller, among the overgrown foliage of government research grants, the HEIG program benefits researchers and capital-tool vendors by paying for equipment that costs more than $750,000. Each one-time grant has a maximum limit of $2 million.
“It’s really critical to research infrastructure that this continues to provide these kinds of resources,” Bushweller said. The university, he said, “would not provide that level of resources for this instrument.”
In addition to HEIG, another program run by NCRR, the Shared Instrumentation Grant Program, helps researchers buy equipment costing between $100,000 and $500,000.
Additionally, the National Science Foundation’s Major Research Instrumentation Program helps researchers pay for instruments costing between $100,000 and $2 million.
But the HEIG program is the only one that provides funding for biomedical instruments, according to Michael Marron, director of the biotechnology division at NCRR.
Since its inception in 2002, HEIG has provided 76 awards and two supplements to institutions in 24 states totaling more than $118 million, according to NCRR’s Web site.
The program was created after researchers told NIH officials that new, expensive technologies were passing them by because they had no funding resources to purchase them. The need for such funding remains critical, Marron said.
“If we had three or four times the amount of money that we make in awards, we could easily spend it on first-rate proposals,” he said. “The demand and need for equipment is enormous.”
For the fiscal year ending Sept. 30, HEIG has a budget of $22 million. President Bush has requested the same amount for the program in his budget proposal for fiscal 2007, which begins Oct. 1.
“If we had three or four times the amount of money that we make in awards, we could easily spend it on first-rate proposals. The demand and need for equipment is enormous.”
Institutions applying for HEIG funds are not required to supply matching funds, but are expected to provide appropriate support for associated infrastructure. In the case of UVa, that includes redesigning a laboratory, adding well-conditioned, uninterrupted power to the lab, and possibly temporarily removing a wall so the spectrometer can be moved into the lab, Bushweller said.
The university is currently accepting bids from vendors for the NMR spec. Bushweller said he expects the instrument to be on-site and operational next spring.
He and his colleagues will use the instrument for the three-dimensional structural study of proteins. The bigger magnet, he said, will provide greater sensitivity, better dispersion of the signals, and improved performance for very large protein systems.
He and the other UVa researchers are particularly interested in studying integral membrane proteins that make up about half of current drug targets.
“These are a very important class of proteins from a pharmaceutical perspective,” Bushweller said. “But there is very little structural information about this class of proteins.”
The facility at UVa currently is equipped with a 600-megahertz spectrometer which has limited capability for the work the researchers want to do. As a result, they’ve had to travel to other facilities in Georgia, North Carolina, and Wisconsin that have the right equipment.
“That class of proteins … in order to carry out structural studies on them, we have to remove them from the biolayer and keep them stable in various detergents,” Bushweller said. “Those protein detergent complexes are very large so the challenges in doing an MR of them are significant, and the higher field allows us to go after those much more effectively.”
Researchers at UCSB and the University of Washington did not respond to requests for interviews. However, in their grant proposal, UCSB researchers said it will use its NMR spectrometer to “work with macromolecules in solution.”
Such work includes “investigation of the structure, function, and dynamics of the proteins involved in bacterial signaling during bacterial chemotaxis and related signaling pathways, protein folding dynamics and the nature of the unfolded state and the structure of self-assembly of RNA-RNA recognition units.”
In their grant proposal, researchers at UW said they will use their multi-tiered proteomic compute cluster to, among other things, fold proteins in vivo, fold proteomes de novo, and “elucidat[e] protein-protein interactions via chemical cross-linking.”
The facility that will house the MPC has a 10-node compute cluster for processing mass spec-based proteomic experiments, researchers said, but none for protein folding.
“The MPC will expand this capability 20-fold. … All aspects of proteomic and protein chemistry-based research will be supported,” the researchers said in their HEIG proposal.