Probing Viral Receptor-Sugar Interactions using Multifunctional Glycan-Nanoparticle


Contact Dr Dejian Zhou to discuss this project further informally.

Project description

Multivalent viral receptor-glycan interactions are central to viral infection and immune response regulation. However, the underpinning structural mechanisms are often poorly understood, due to a lack of effective probes for such complex, multimeric and flexible proteins. Herein we will develop polyvalent glycan-nanoparticles (NPs) with tuneable glycan valency & flexibility as novel structural probes for two closely related, almost identical tetrameric receptors, DC-SIGN/R, which bind to the HIV/Ebola virus surface sugars to enhance viral infection.[1]

However, how their four carbohydrate-recognition-domains (CRDs) are spatially arranged remain unclear. This information is key to their specific binding to viral surface glycans and viral trans-infection. We hypothesis that a perfect spatial match between the NP surface multiple glycans and protein binding sites will result in high affinity multivalent binding, allowing us to derive the CRD arrangement.[2]

This project includes four objectives:

1) synthesise & characterise dihydrolipoic acid-PEG-sugar based multifunctional ligands;
2) produce site-specifically labelled DC-SIGN/R;
3) prepare & characterise polyvalent sugar coated NPs and study their binding affinity and specificity with DC-SIGN/R by FRET[3], and
4) investigate their inhibition of virus infection of DC-SIGN/R expressing host cells and correlate their binding affinity with viral inhibition potency. This study will not only yield important structural information about these vial receptors but also lead the development of potent multivalent glycan-nanoparticle inhibitors that can block the viral entry to target cells, thereby preventing deadly viral infections.

Reference [1]. Geijtenbeek, T. B. H., et al. (2000) Cell 100, 587-597; Guo Y, et al. (2004) Nat. Struct. Mol. Biol. 11, 591-598. [2]. Guo, Y., et al. (2016) Angew. Chem. Int. Ed. 55, 4738-4742. [3]. Guo, Y., et al. (2017) J. Am. Chem. Soc. 139, 11833-11844.

Entry requirements

Applications are invited from candidates with or expecting a minimum of a UK upper second class honours degree (2:1), and/or a Master's degree in a relevant subject.

Additional staff contact

Dr Yuan Guo and Professor Bruce Turnbull

How to apply

Formal applications for research degree study should be made online through the university's website. Please state clearly in the research information section that the PhD you wish to be considered for is the ‘Probing Viral Receptor-Sugar Interactions using Multifunctional Glycan-Nanoparticle’ as well as Dr Dejian Zhou as your proposed supervisor.

If English is not your first language, you must provide evidence that you meet the University’s minimum English Language requirements.

If you require any further information please contact the Graduate School Office

We welcome scholarship applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.