Brett Alcott
BA, Cornell University (Chemistry, Biochemistry)
MA, M.Phil., Columbia University (Biophysics)

My work aims to better understand the protein-lipid interplay underlying the fusion of enveloped viruses, such as influenza, ebola and HIV with host cells. Viral infection necessarily involves the injection of genetic material into the host. I am most interested in how the fusion pore – the initial narrow connection between the viral and cell membranes – nucleates, and the driving forces that promote or retard pore dilation. A molecular understanding of the mechanism of viral membrane fusion will aid in the development of antivirals that target critical intermediates of this early stage in the pathway to infection.

In this project I employ a combined optical and electrophysiological approach to dissect this crucial stage of the host/pathogen interface in-vitro. Through the use of cells expressing viral fusion proteins, such as influenza hemagglutinin (HA) and nanodiscs – artificial membranes of controllable size and molecular composition – I plan to study fusion events in real time, with millisecond resolution at the level of a single pore. In particular, this experimental approach will enable us to test hypotheses about how intra- and inter-molecular interactions and parameters such as tension affect both the pathway to fusion and the dynamics of the fusion pore. In collaboration with the O’Shaughnessy lab at Columbia University, these experimental findings will provide input and feedback for computer simulations of the fusion process.