Structural Investigation of Viral Surface Glycoproteins

Viral surface glycoproteins are essential to viral replication cycles, mediating viral entry and escape. However, their surface exposure renders them key immunological targets and the centre of most vaccine designs. A comprehensive structural understanding of surface viral glycoproteins is therefore needed to understand their recognition by broadly neutralising antibodies (bnAbs) which are ideally produced in response to vaccination. This research will engage two high-priority viral pathogens, namely Human immunodeficiency virus (HIV) and Rift Valley Fever Virus (RVFV). The aims of this work will be two-fold. For HIV-1 there remain key questions surrounding its glycoprotein biology which have significant implications for future vaccine design. We will investigate these questions by cryo-EM of native HIV-1 Envelope (Env) glycoprotein. Secondly, RVFV vaccines are under trial and remain to be studied from a structural mechanistic standpoint. Therefore, I will seek to understand how the nChAdOx1 RVF vaccine is working at the molecular level to elicit protective antibody responses in patients.