PhD Studentship funded by BBSRC DTP Program

Evaluating and modelling glycosaminoglycan fragment interactions with COVID-19

Available for Sept 2022 start. Application now open; deadline January

Oligosaccharides are ubiquitous biomolecules on cell surfacesand 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. It is likely to present opportunities to expand applications to other related targets and will work closely and benefit from our other ongoing projects in the areas of GAG fragment interactions, COVID proteins and liposomal constructs.

 

Work will involve chemical synthesis (Gardiner lab), liposome conjugate technology (Webb lab), protein studies (Jeremy Derrick group, Life Sciences) and computational modelling (Jim Warwicker lab, MIB).

Informal email enquiries are very welcome. 

 

• 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. 

• Hebditch, M.; Warwicker, J. “Protein-sol pKa: prediction of electrostatic frustration, with application to coronaviruses.” Bioinformatics2020, 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.

Research Associate in Carbohydrate Chemistry/Chemical Biology _FILLED

Job Reference : S&E-14815

Location : Manchester Institute of Biotechnology and Department of Chemistry, University of Manchester

Closing Date: 03/12/2019

Salary : £ Grade 6 £32,816 to £40,322 per annum

Employment Type : Fixed Term

Faculty / Organisational Unit : Science & Engineering 

Division : Chemistry

Glycoscaminoglycan oligosaccharides (GAGs) are essential to many critical biological processes, including cell-differentiation, cancer, bacterial and viral infections and inflammation, so there is major interest in advancing our understanding of the chemical biology and biomolecular interactions of these structures. This project aims to develop a platform of synthetic GAG structures to interrogate the H/HS interactome, which will provide unprecedented details of GAG biomolecular interactions It is a collaboration between University of Manchester, Department of Chemistry and the School of Chemistry, University of Glasgow; there will  be an allied biophysical PDRA positon at the University of Glasgow. Applications are invited for the postdoctoral position at the University of Manchester, which aims to synthesise carbohydrate (oligosaccharide) targets as tools for chemical biology.

This Manchester position will involve the synthesis of GAG oligosaccharides and conjugates and their use for liposome labelling and other nanoscale applications, such as chemical biology tools for native and mutant GAG-binding proteins. The work will develop chemical and biocatalytic methods for conjugation. This post will be primarily based in the synthetic chemistry labs in the Manchester Institute of Biotechnology (http://www.mib.ac.uk), an internationally-leading state-of-the-art building for research in interdisciplinary biologically-related science. The successful applicant will be part of a team involving carbohydrate synthesis (Gardiner: www.gardinergroup.org.uk), liposome applications and biophysical studies (Webb: www.webblab.org), and biocatalytic carbohydrate modification (Flitsch: www.flitschlab.com). The project is ideally-suited for applicants keen to explore multidisciplinary applications, including biophysical studies using liposomes, protein science and also exploring and evaluating biocatalytic oligosaccharide modifications. The Glasgow position (separately advertised through UoG, supervised by Dr S Magennis) will involve single-molecule spectroscopic method development and applications. The Manchester PDRA will have regular contacts within the UoG team and be involved in project planning meetings.

Applicants should have a PhD (or equivalent) in synthetic or bioorganic chemistry / chemical biology and must have experience in carbohydrate synthetic work. Experience of labelling chemistry and/or multidisciplinary work would be an advantage, though not essential. The appointee must have demonstrated the ability to produce leading research outputs. Evidence of managing research projects previously would be an advantage.

The School of Chemistry is strongly committed to promoting equality and diversity, including the Athena SWAN Charter for gender equality in higher education.  The School holds a Silver Award which recognises their good practice in relation to gender; including flexible working arrangements, family-friendly policies, and support to allow staff to achieve a good work-life balance.  We particularly welcome applications from women for this post. Appointment will always be made on merit.  For further information, please visit http://www.chemistry.manchester.ac.uk/about-us/athena-swan/

Please note that we are unable to respond to enquiries, accept CVs or applications from Recruitment Agencies.

Informal enquiries about the project, vacancy shortlisting and interviews:

Name: Dr John Gardiner

Email: gardiner@manchester.ac.uk

 

Technical support:

Email: universityofmanchester@helpmeapply.co.uk

Tel:      0161 850 2004

 

General enquiries:

Email: hrservices@manchester.ac.uk

Tel:      0161 275 4499

This vacancy will close for applications at midnight on the closing date

 

Further Particulars and Full Job Description at:

S&E-14815 Research Associate in Carbohydrate Chemistry/Chemical Biology ;