Running the Gamut: From Structural Biology to HIV-1 Vaccine Design

Abstract

Transmembrane proteins are major drug targets in bacteria, viruses, and humans. Utilizing a combination of single-particle electron microscopy, mass spectrometry, and numerous other biophysical and biochemical techniques, my thesis work has elucidated the structures and mechanisms of multiple membrane protein complexes. Specifically, the work encompassed by this dissertation focuses on uncovering the structure and mechanism of (i) a novel pathogenic bacterial ion channel, (ii) understanding the structural requirements and mode-of-action of a therapeutic antibody in complex with an angiogenic human integrin receptor, and (iii) determining the immune recognition pattern of the HIV viral spike glycoprotein for vaccine design purposes. This work aims to shed important structural and functional insights on membrane protein drug targets and their associated underlying diseases.