After growing up nearby in Huddersfield, I went to the University of Bristol to do an Integrated Master’s Degree in Chemistry. There, I thoroughly enjoyed organic chemistry, as well as all of the interdisciplinary topics I was fortunate enough to study. My Master’s project involved the synthesis of glycan-based molecules which could act as probes for Mycobacterium Tuberculosis. I knew then that I wanted to continue working in a lab to work on the early stages of developing therapeutics with my chemistry background. This is exactly what I came to do at Leeds, but from a more interdisciplinary approach. I get to use my skills in a chemistry lab, as well as explore areas of biology and biophysics both in my reading and in experiments.
Binding of pathogen surface specific glycans by immune cell surface lectins is the first step to activate immune defences against infection. However, some pathogens have developed strategies to exploit such recognitions to modulate immune cell responses to facilitate infection. The HIV surface is decorated with heavily glycosylated proteins with unusually large inter-glycoprotein distances, and binding of HIV by a dendritic cell (DC) surface lectin, DC-SIGN, allows the HIV to evade intracellular degradation and facilitate infection. However, mechanisms underlying how specific DC-SIGN-glycan interactions modulate DC immune response remain unclear. As multiple such interactions are involved and DC-SIGN has shown to form clusters on DC surface, we hypothesise that pathogens use their specific glycan patterns to control DC-SIGN cluster formation and stability as a way to modulate DC-SIGN signalling, and hence DC immune outcomes.
We plan to develop novel glycan-nanoparticles as multifunctional pathogen mimics to probe pathogen-DC interactions. To do this, we synthesise non-toxic gold nanoparticles and coat them with oligomannose (found on HIV), varying their surface glycan valency inter-glycan spacing. To fill a current research gap, we can mimic the natural presentation of DC-SIGN on cell membrane by anchoring the protein onto supported lipid bilayers and quantify their binding by quartz crystal microbalance and spectroscopic ellipsometry. This will reveal the difference and correlation between multivalent bindings in solution and on surfaces and help to develop effective immunotherapies against infectios diseases like HIV.