NIH grants will advance studies of the form and function of proteins
The National Institutes of Health has awarded 23 grants for structural biology research totaling up to $290 million over five years. The projects will focus on determining the shapes and functions of proteins important in biology and medicine.
The awards are part of the Protein Structure Initiative (PSI), an effort that started in 2000 with the main goal of developing highly efficient, or high-throughput, methods for revealing the structures of many different proteins. The structures help scientists answer questions about protein biology and model other structures.
With these new grants, the PSI begins its third five-year phase, PSI:Biology. A key aim is to utilize the high-throughput methods developed during the PSI’s first decade to generate protein structures for functional studies.
“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,” said Jeremy M. Berg, Ph.D., director of NIH’s National Institute of General Medical Sciences, which funds the PSI. “Now it’s time to deploy these capabilities so we can advance our understanding of the role proteins play in health and disease.”
Four large-scale PSI:Biology centers will operate pipelines for determining protein structures nominated by the scientific community or identified by collaborating biologists funded by PSI:Biology grants. The centers, all established during the first phase of the PSI, are based in California, Illinois, New Jersey and New York and will receive up to $140 million in funding.
These centers will partner with eight groups of researchers that require the determination of many protein structures to understand biological processes or a molecule’s function. These grants total up to $75 million.
For example, John Markley, Ph.D., at the University of Wisconsin-Madison will work with the large-scale centers to map all the unique proteins associated with mitochondria, the energy factories of cells that are also involved in a number of human diseases.
PSI:Biology also will support nine centers for determining membrane protein structures. These proteins, embedded in the membrane of our cells, are important because they enable our nerves, muscles and hormones to do their jobs. Scientists, however, can’t easily visualize their three-dimensional shapes to better understand how these proteins function. The membrane protein centers, similar to the large-scale centers, will focus on solving the structures by developing highly efficient methods and by collaborating with PSI:Biology partners as well as scientists outside the research network. These centers will receive up to $75 million.
“The value of membrane proteins in biology and medicine has been clear for a long time, and now we need to take a major step toward making membrane protein structure determination better, faster and cheaper, just as the PSI has done for many other types of proteins,” said Ward Smith, Ph.D., PSI director.
For instance, the membrane protein center led by Ray Stevens, Ph.D., at the Scripps Research Institute in La Jolla, Calif., will focus on a special class of membrane proteins called G protein-coupled receptors (GPCRs) that serve as the target for more than half of all therapeutic drugs. Stevens will develop new methods and technologies for generating high-resolution structures of nearly two dozen GPCRs from a wide range of organisms, including humans, for use in both basic and applied biomedical research.
For the complete list of awards, see the PSI:Biology Network page at http://www.nigms.nih.gov/Initiatives/PSI/psi_biology/.
Additional investigators will join the PSI:Biology network through ongoing funding opportunities to partner with the high-throughput centers or to develop new methods and approaches for protein modeling and structure determination.
Two other key components of PSI:Biology are the PSI Structural Biology Knowledgebase, which collects and disseminates PSI data, proteins, publications, technologies and other developments, and the PSI Materials Repository, which centralizes, maintains and distributes vectors and clones produced by PSI investigators. Both resources were established during the second PSI phase to serve the broader scientific community.