The 2017 Mathilde Krim Fellowships in Basic Biomedical Research Grants
PI: Daniela Monaco, Ph.D.
Mentor: Eric Hunter, Ph.D.
Impact of pre-adaptation on viral evolution and virus control in newly infected individuals
Dr. Daniela Monaco’s work in the field of HIV evolution has taken her around the world from her native Argentina to South Africa, France, Trinidad & Tobago and now Atlanta, Georgia, where she works in the lab of Dr. Eric Hunter as a postdoctoral scientist.
Dr. Monaco plans to bring insights from vaccine development to bear on attempts to cure HIV, thus uniting two fields traditionally seen as operating at opposite ends of the spectrum of research aimed at ending HIV/AIDS. From the earliest moments of infection, the immune system exerts pressure on the virus, which responds by mutating to evade that pressure, setting off a spiral of virus mutations and immune system responses. When that virus is transmitted to a new host, a new spiral is set in motion, whereby the ability of the immune system to control the virus is partly determined by how well the immune responses match from one host to another. Dr. Monaco plans to use blood samples from transmission pairs her team has gathered in Zambia to analyze the accumulation of mutations before and after transmission. She hopes to identify parts of the virus that are consistently resistant to mutations and to exploit these vulnerabilities to target the cells of the viral reservoir.
PI: Gabriel Ozorowski, Ph.D.
Mentor: Andrew Ward, Ph.D.
The Scripps Research Institute
Exploiting dynamic conformational states of HIV-1 Env as targets for novel inhibitors
Dr. Gabriel Ozorowski has been fascinated by the intersection of computational and structural biology since he was a graduate student at the University of California, Irvine. In the lab of Dr. Andrew Ward at The Scripps Research Institute, where he is currently a postdoctoral scientist, Dr. Ozorowski has co-authored over two dozen publications on electron microscopy of viral proteins.
In 2003, the FDA approved the first and only fusion inhibitor for the treatment of HIV. Dr. Ozorowski’s work may change that by bringing together cutting-edge computational biology with cryoEM—a technique that reveals detailed structures of molecules by freezing them at -180° C. Using cryoEM, Dr. Ozorowski is discovering previously unknown structures of Env, the viral protein that is the target of fusion inhibitors. With the novel Env structures in hand, Dr. Ozorowski can employ algorithms in computational biology to conduct a virtual screen through hundreds of thousands of small drug molecule libraries. He hopes to identify those that are predicted to perturb the newly discovered Env structures and thus develop new fusion inhibitors.
PI: Jonathan Richard, Ph.D.
Mentor: Andrés Finzi, Ph.D.
Université de Montréal, Centre de Recherche du CHUM
Harnessing NK cell responses to eliminate HIV-1 infected cells
Dr. Jonathan Richard, recipient of the prestigious Frederick Banting and Charles Best Canada Graduate Scholarship Award, is conducting his postdoctoral training under the mentorship of Dr. Andres Finzi, a previous Krim Fellow, at the Centre de Recherche du CHUM within the Université de Montréal. In only four years of postdoctoral work, Dr. Richard has co-authored an impressive 21 publications and has built collaborations with leaders in the vaccine field through his participation in CHAVI-ID, an important HIV vaccine consortium.
Natural killer (NK) cells destroy virally infected cells through at least two mechanisms and are thus of interest for HIV cure strategies. HIV uses some of its own proteins to avoid being targeted by NK cells, but Dr. Richard has found two host proteins that enhance both of these killing mechanisms. He will explore the effects of boosting these host proteins on each of the NK killing mechanisms to determine whether they can be used as part of a strategy to kill the cells of the viral reservoir.