Probing Viral Receptor-Sugar Interactions using Multifunctional Glycan-Nanoparticle

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. The earliest start date for this project is 1 October 2020.

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/info/130206/applying/91/applying_for_research_degrees">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &lsquo;Probing Viral Receptor-Sugar Interactions using Multifunctional Glycan-Nanoparticle&rsquo; as well as <a href="https://physicalsciences.leeds.ac.uk/staff/199/professor-dejian-zhou">Professor Dejian Zhou</a>&nbsp;as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome 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.</em></p>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<p><strong>Self-Funding Students</strong></p> <p><strong>Funding Eligibility</strong></p> <p><strong>UK/EU</strong> &ndash;&nbsp;Leeds Doctoral Scholarship Award paying Academic Fees and Maintenance matching EPSRC rate of &pound;15,009 per year for 3 years, Lowson Research Scholarship&nbsp;paying Academic Fees and Maintenance at a fixed rate of &pound;14,000 per year for 3 years, School of Chemistry Scholarship award paying Academic Fees and Maintenance matching EPSRC rate of &pound;15,009 per year for 3 years.&nbsp; Alumni Bursary is available to previous University of Leeds graduates offering 10% discount on Academic Fees.</p> <p><strong>International Students</strong> &ndash;&nbsp;China Scholarship Council-University of Leeds Scholarship Award paying Academic Fees for 3 years,&nbsp;School of Chemistry Scholarship award paying Academic Fees for 3 years, Commonwealth Scholarship and Commonwealth Split Site Scholarships.&nbsp; Alumni Bursary is available to previous University of Leeds graduates offering 10% discount on Academic Fees.</p>

<p>For further information regarding your application, please contact Doctoral College Admissions by&nbsp;email: <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions</a><a href="mailto:EMAIL@leeds.ac.uk">@leeds.ac.uk</a>, or by telephone: +44 (0)113 343 5057.</p> <p>For further information regarding the project, please contact Professor Dejian Zhou by email:&nbsp;&nbsp;<a href="mailto:D.Zhou@leeds.ac.uk">D.Zhou@leeds.ac.uk</a></p>