PITTSBURGH, Aug. 27 – The National Institutes of Health (NIH) announced today that it is awarding the University of Pittsburgh School of Medicine a $16 million, five-year grant to establish the Pittsburgh Center for HIV Protein Interactions (PCHPI). Research at the center will give scientists detailed new insights into the life of HIV, the virus that causes AIDS, and have important implications for developing new drug targets.
One of three centers being funded jointly by the National Institute of General Medical Sciences (NIGMS) and the National Institute of Allergy and Infectious Diseases (NIAID), the PCHPI will specialize in developing methods and tools for understanding what happens to the HIV virus, both structurally and at an atomic level, immediately after it enters the cell and prior to becoming integrated into the host genome. By doing this, PCHPI researchers will be able to identify which cellular processes and components are hijacked by HIV for its nefarious purposes.
“We know how HIV attaches to its host and how it gains entry to cells, but what happens between when it first enters into the cells and when it integrates itself into the host genome is still a mystery. By elucidating the important events during this period, we believe we’ll learn a great deal about the how the virus can be stopped,” said PCHPI director, Angela Gronenborn, Ph.D., the University of Pittsburgh Medical Center Rosalind Franklin Professor and chair of the department of structural biology, University of Pittsburgh School of Medicine. Dr. Gronenborn, who recently was elected to the National Academy of Sciences, is one of the country’s leading structural biologists and an internationally renowned specialist in the application of nuclear magnetic resonance (NMR) spectroscopy for investigating the biochemical mechanisms and cellular structures involved in HIV pathogenesis. The other two NIH-funded HIV structural biology centers are led by Alan Frankel, Ph.D., a biochemist at the University of California, San Francisco, and Wesley Sundquist, Ph.D., a biochemist at the University of Utah.
Although researchers have determined the structures of many HIV proteins in isolation, they know the structures of only a few HIV proteins in their functional state, that is, when they interact with cellular components of host cells. Because HIV works through such interactions, knowing their structures will provide targets for new generations of anti-AIDS drugs. Center researchers will use NMR and X-ray crystallography to identify and characterize atomic structures of key virus interactions and other pivotal events in the immediate post-entry stage of the viral life cycle. They also will use advanced imaging technologies such as cryo-electron tomography to better study the structure of HIV and the host cellular components with which it interacts.
As part of its mission to collaborate with researchers nationally and globally, the center will make the methods and tools it develops available to the HIV research community at large. These resources are expected to have major impact in the global fight against AIDS, which is estimated to afflict more than 40 million people worldwide.
“HIV is so challenging to treat because the virus is extremely adept at evolving resistance against therapies that target individual HIV proteins. Efforts by Dr. Gronenborn and her colleagues to identify and image pivotal virus-host cell interactions could forge new avenues for drug discovery,” explained Ravi Basavappa, Ph.D., the NIGMS program director for the new centers.
In addition to studying the structure and interactions of HIV using advanced technologies, another focus of the center will be to engage virologists, cell biologists and structural biologists in a collaborative effort toward deciding which of these interactions make the best drug targets.
“For many years, structural biologists and virologists have not worked closely in the area of HIV-targeted drugs. This center will allow the two to work collaboratively and help them to determine fairly quickly whether their hypotheses about what happens at the molecular and atomic levels of HIV infection are accurate,” said Dr. Gronenborn.
The University of Pittsburgh School of Medicine is considered among the nation’s leading medical schools, renowned for its curriculum that emphasizes both the science and humanity of medicine and its remarkable growth in National Institutes of Health (NIH) grant support, which has more than doubled since 1998. For fiscal year 2005, the University ranked seventh, out of more than 3,000 entities receiving NIH support, with respect to the research grants awarded to its faculty. The majority of these grants were awarded to the faculty of the medical school. As one of the university’s six Schools of the Health Sciences, the School of Medicine is the academic partner to the University of Pittsburgh Medical Center. Their combined mission is to train tomorrow’s health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care.