Probing Viral Receptor-Glycan Interactions using Polyvalent 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 and 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]<br /> <br /> 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]<br /> <br />

<p>This project includes four objectives:</p> <p>1) synthesise & characterise dihydrolipoic acid-PEG-sugar based multifunctional ligands;<br /> 2) produce site-specifically labelled DC-SIGN/R;<br /> 3) prepare & characterise polyvalent sugar coated NPs and study their binding affinity and specificity with DC-SIGN/R by FRET[3], and<br /> 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.</p> <p>Reference [1] Geijtenbeek, T. B. H., et al. (2000) Cell 100, 587; Guo Y, et al. (2004) Nature Struct. Mol. Biol. 11, 591. [2] Guo, Y., et al. (2016) Angew. Chem. Int. Ed. 55, 4738. [3] Guo, Y., et al. (2017) J. Am. Chem. Soc. 139, 11833. [4] Budhadev et al. (2020) J. Am. Chem. Soc. 142, 18022.</p>

<p>Formal applications for research degree study should be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University's website</a>. Please state clearly in the Planned Course of Study that you are applying for <em><strong>PHD Chemistry FT</strong></em> and in the research information section that the research degree you wish to be considered for is <strong><em>P</em></strong><em><strong>robing Viral Receptor-Sugar Interactions using Multifunctional Glycan-Nanoparticle </strong></em>as well as <a href="https://physicalsciences.leeds.ac.uk/staff/199/professor-dejian-zhou">Professor Dejian Zhou</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <p style="margin-bottom:11px"><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p> <p class="MsoNoSpacing">Applications will be considered on an ongoing basis.  Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application.  We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed.</p> <p>Please note that you must provide the following documents at the point you submit your application:</p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> <li>Funding information including any alternative sources of funding that you are applying for or if you are able to pay your own fees and maintenance</li> </ul> <p> </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 style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong> – The <a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Non-UK</strong> –The <a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a> is available to nationals of China. The <a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a> is available to support US citizens. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Important:</strong>  Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are <strong>not</strong> covered under these studentships.</p> <p>Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p>

<p>For further information about your application, please contact Doctoral College Admissions: e: <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions</a><a href="mailto:EMAIL@leeds.ac.uk">@leeds.ac.uk</a></p> <p>For further information about this project, please contact Professor Dejian Zhou: e:  <a href="mailto:D.Zhou@leeds.ac.uk">D.Zhou@leeds.ac.uk</a></p>