Biochemical Study of a HIV-1 Gag-PR Resistance Mechanism

Sebastian Breuer, The Scripps Research Institute, La Jolla
Mentor: Bruce Torbett
Basic Biomedical Sciences
Postdoctoral Fellowship Award

The pandemic of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) remains an unsolved scientific and medical problem. The research effort since the early 1980s led to a therapeutic strategy that renders an improved and prolonged lifespan, but it in the moment there is no cure, no vaccination and only limited therapy options for AIDS. Moreover, many patients fail therapy and have to change their regimen due to a phenomenon called drug resistance. This is a widely spread problem among HIV positive patients that demands an extensive monitoring of therapy and consequently adjustment of treatment. It is known that HIV is a highly versatile virus but how the virus escapes the cocktail of antiretroviral drugs remains to be clarified. Our goal is the investigation of drug resistance development and definition of a general paradigm that allows the prediction of therapy failure and improvement of therapy...

In the past, we developed a novel technique that allows studies of an important viral process at a molecular level. Together with scientist at the University of California, San Diego (UCSD) and The Scripps Research Institute (TSRI) we intend to employ this technique to learn more about the underlying mechanism and make suggestions for future strategies. Moreover, we will pursue first steps towards new HIV therapeutics by employing the novel technique for dug discovery and inhibitor development. Many molecular processes during the HIV life cycle represent potential targets for current drug development. In collaboration with chemists at TSRI we will focus on a key function during virus production and provide new small compounds that potentially could be part of the antiviral drug pool.