2023
The title of my project is “Elucidating molecular dynamics of human endogenous fatty acid synthase to stagnate HIV replication”. My primary goal is to unveil structural and functional correlation of human fatty acid synthase in the physiologically relevant environments, such as the correlation between the conformational dynamics and the catalytic cycle of the protein.
Broadly, human fatty acid synthase in cells is a nano factory that de novo synthesizes lipid molecules, which is required for viral replication, including HIV. I developed an efficient CRISRP-based knock-in protocols to tag endogenous proteins in various human cell lines for structural studies. Thus, this project also aligns with the “from endogenous tagging to structure” pipeline that HARC center is establishing.
Most structural studies portray one or more snapshots of target proteins to understand their mechanisms. However, the fatty acid synthase shows extreme conformational dynamics, makes it difficult to dissect the relationship between the conformational dynamics and its function. By applying state-of-the-art single particle cryoEM and a newly developed data analysis algorithm in the lab, I will dissect molecular dynamics of subdomains and generate continuous snapshots, like a movie, to illustrate the correlation. This information could potentially be used for development of new therapeutic strategies targeting fatty acid synthase.
During viral infections, host proteins are often hijacked to facilitate viral replication. Therefore, continuous research efforts on viral – host protein complexes are of vital importance to the development of new therapeutic strategies or targets. My work will hopefully facilitate this effort.
