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(BBSRC DTP) Evaluating and modelling glycosaminoglycan fragment interactions with COVID-19


Department of Chemistry

About the Project

Oligosaccharides are ubiquitous biomolecules on cell surfaces and the intra-cellular matrix, and are central to many critical biological regulatory processes, including cell-differentiation, cancer, bacterial and viral infections and inflammation. In particular, glycosaminoglycan oligosaccharides (GAGs), such as heparin / heparin sulfate (H/HS), are essential to many such processes, so there is major interest in advancing our understanding of the chemical biology and biomolecular interactions of these structures. H/HS-type GAGs have been recently seen as able to bind to COVID-19 and have potential to inhibit viral infection.
This project involves an exciting multidisciplinary combination of synthetic carbohydrate chemistry and derived glycoconjugates to investigate and characterize specific interactions of synthetic GAG fragment entities (single molecule and liposomal displays) with COVID-19 protein targets. The synthesis and use of pure synthetic GAG-fragments and modified derivatives will be used in conjunction with both experimental and theoretical COVID protein studies. The project will provide an exciting opportunity for working across a multidisciplinary team to build on technologies developed at the University of Manchester, collaborating closely with ongoing projects in these areas both here and at other UK Universities.

http://www.gardinergroup.org.uk
https://www.research.manchester.ac.uk/portal/jeremy.derrick.html
https://personalpages.manchester.ac.uk/staff/j.warwicker/
http://www.protein-sol.manchester.ac.uk

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

MIB

Funding Notes

Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

• Jeanneret, R. A.; Dalton, C. E.; Gardiner, J. M. “Synthesis of Heparan Sulfate- and Dermatan Sulfate-Related Oligosaccharides via Iterative Chemoselective Glycosylation Exploiting Conformationally-Disarmed [2.2.2] L-Iduronic Lactone Thioglycosides. “ J. Org. Chem., 2019, 84, 15063-15078.
[directly underpinning methods]
• Hebditch, M.; Warwicker, J. “Protein-sol pKa: prediction of electrostatic frustration, with application to coronaviruses.” Bioinformatics, 2020, doi: 10.1093/bioinformatics/btaa646. Online ahead of print.
Zuzic, L.; Marzinek, J.K.; Warwicker, J.; Bond, P.J. “A benzene-mapping approach for uncovering cryptic pockets in membrane-bound proteins.” J. Chem. Theory Comput., 2020, 16, 5948-5959.
• Aston-Deaville, S.; Carlsson, E.; Saleem, M.; Thistlethwaite, A.; Chan, H.; Maharjan, S.; Facchetti, A.; Feavers, I. M.; Siebert, C. A.; Collins, R.; Roseman, A.; Derrick, J. “An assessment of the use of Hepatitis B Virus core protein virus-like particles to display heterologous antigens from Neisseria meningitides.”
Vaccine 2020, 38, 3201-3209.
• Zawawi, A.; Forman, R.; Smith, H.; Mair, I.; Jibril, M.; Albaqshi, M. H.; Brass, A.; Derrick, J. P.; Else, K. J. "In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection." PLoS pathogens 2020, 16, e1008243.
• Craven, F.; Silva, J.; Segarra-Maset, MD.; Huang, K.; Both, P.; Gough, J.; Flitsch, S.; Webb, S.
‘One-pot’ sequential enzymatic modification of synthetic glycolipids in vesicle membranes
Chem. Commun., 2018, 54, 11, 1347-1350.

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