PhD Studentship funded by BBSRC DTP Program 2024
Toolkit for evaluation of glycosaminolglycan and fragment bacterial protein interaction studies
Available for Sept 2024 start. Application now open; deadline January
Oligosaccharides are critical carbohydrate-based biomolecules found widely on cell surfaces and the intra-cellular matrix, central to many vital biological regulatory processes, including cell-differentiation, cancer, bacterial and viral infections and inflammation. In particular, glycosaminoglycans (GAGs), eg heparin / heparin sulfate (H/HS), dermatan sulphate (DS), chondroitin sulfate (CS), are essential to many such processes, so there is major interest in advancing understanding of the chemical biology and biomolecular interactions of these structures. GAGs have previously been identified in cell-attachment process for viral and bacterial pathogens. Defined synthetic GAG fragments are important to develop understanding of such interactions. This project involves a multidisciplinary combination of synthetic carbohydrate chemistry and derived glycoconjugates to investigate interactions with bacterial adhesion proteins. These technologies will be applied to the study of the binding specificities and recognition of GAGs by selected bacterial cell surface proteins. These proteins play a critical role in mediating adhesion to endothelial and epithelial cells but the basis for their specificities is poorly understood at the molecular level. This project will use the range of synthetic GAGs to examine how ligand binding specificities differ between different cell surface proteins from different organisms and how these properties are related to pathogenicity.
​
Work will involve synthesis of pure synthetic GAG-fragments, and protein production and interaction studies working across a multidisciplinary team with synthetic, biological and biophysical expertise. This project is underpinned by work developed at Manchester, to produce diverse, structurally-defined pure GAG-type structures, carry out biological evaluations, examine recognition of long GAGs, and demonstrate that defined HS-sulfation encoding can provide dramatic changes in biological effects.1,2 The team includes international expertise in liposome technology and its applications to biomolecules.3 and bacterial adhesion and vaccine development approaches.4,5
​
This project will involve collaborating closely with ongoing projects providing experience across a range of chemical and biotechnology areas.
The work will involve activities in the Chemistry Department (Gardiner/Webb labs) and Biological Sciences (Derrick group), which are all located in close proximity in central campus.
​
Infrormal enquiries welcome for further info. You can send email via the email links on this website.
[1] J. Org. Chem. 2019, 84, 15063-15078 and refs therein.
[2] Nature Commun. 2013, DOI: 10.1038/ncomms3016; Chemical Science 2013, 4, 3218-3222; 2015, 6, 6158-6164; Chem. Commun. 2015, 51, 13846-13849.
[3] J. Mater. Chem. B, 2022, 10, 5016-5027.
[4] PLoS pathogens 2020, 16, e1008243. [5] Npj Vaccines 8 (2023); mSphere 7, e00674-21 (2022); J. Infection 84, 658-667. (2022).
PhD Studentship funded by BBSRC DTP Program 2023
Synthesis, applications and modelling glycosaminoglycan fragment interactions with COVID-19
Available for Sept 2023 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. Work will involve deign and applications of conjugates being developed in Manchester. The work is aimed at a platform that woud have applications to variants of COVID but also provide important technology portable to other viral threats.
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. The project has 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 in our labs, 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).
​
The Gardiner and Webb labs are based in the Chemistry Department main research building, which is based in central campus near the Main University building and park. The Derrick and Warciker groups are based in Life Sciences, in buildings close to Chemistry on central campus.
​
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.” 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.
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 ;