Associate Prof Weston Struwe

Associate Prof Weston Struwe

Understanding mechanisms of host-virus interactions across molecular scales

Our research focuses on virus glycoproteins and how their structure and dynamics contribute to immune recognition, vaccine efficacy and host cell entry. Enveloped virus glycoproteins are among the most glycosylated in nature and their glycan structures can be viewed as molecular “keys” that fine-tune various biological functions through seemingly diminutive changes in their biophysical properties. We believe this functional regulation is both specific and widespread across biology, but most conventional methods cannot fully unpick these relationships to understand how glycan participate in human health and disease. Therefore, our approach for understanding how viruses function is underpinned by creating advanced tools in mass spectrometry, mass photometry as well as glycoprotein engineering strategies that can derive exceptional insights in complex infection processes.

Our objective is to learn how host and viral proteins communicate and interact during infection, primarily Ebola, Nipah and HIV-1, with the goal of answering the following fundamental questions:

1. What are the mechanisms of antibody-mediated neutralisation and viral spike recognition?
2. What is the role of receptor binding cooperativity and multivalency in viral fitness?  
3. In addition to virus attachment factors, which glycosaminoglycans serve as inhibitors?
4. How are viral proteins glycosylated and what is the functional relevance of specific glycans?
5. Can we exploit biorthogonal click chemistry to track virus glycoprotein interactomes? 

Answering these questions is profoundly important for the design of vaccines, efficacy of antibody therapies as well as for learning how viruses function and how our immune system responds to infection. However, glycoproteins pose a unique challenge in structural biology and part of our work aims to overcome their inherent complexity to pin-point individual glycan structures, present among hundreds or more proteoforms, that are responsible for specific biological disease processes via the interactions they facilitate. Mass spectrometry is our principal methodology and we are advancing new technologies based on ion mobility, electrospray ion-beam deposition with scanning probe microscopy, hydrogen-deuterium exchange, chemical crosslinking and native MS for studying glycoproteins. Combined with mass photometry, a single-molecule imaging technique capable of tracking protein assemblies on membrane surfaces, we can derive a complete structural and biophysical picture how virus glycoproteins function – from glycan structure to macromolecular assembly.

To find out more visit our lab website; https://struwe.web.ox.ac.uk