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Mining the human gut microbiome for novel industrially relevant glycoenzymes


Biosciences Institute

Dr D Bolam , Prof D Rigden , Dr Jon Marles-Wright Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Biochemistry Bioinformatics Molecular Biology Structural Biology

About the Project

Cell surface glycans play essential roles in many important biological processes. Inter-individual variations in glycan composition are large, and these differences associate with disease risk, disease course and the response to therapy. In addition, cancer cells often express altered surface glycan profiles to avoid the immune system and enhance malignancy.

A key part of the personalised medicine revolution is to be able to identify specific disease biomarkers (e.g. altered glycosylation patterns), quickly and accurately to enable the medication to be tailored to the patient. Carbohydrate active enzymes (CAZymes) are often used to analyse and identify discrete glycan structures as biomarkers, but there is a growing need for new enzyme activities to improve specificity for the structures targeted and provide enhanced biomarker detection.

This CASE studentship is a collaboration between labs at Newcastle (Dr David Bolam and Dr Jon Marles-Wright) and Liverpool (Prof Dan Rigden) Universities and Ludger Ltd (Oxford) to exploit the huge untapped resource of potential novel human-glycan active enzymes encoded by the human gut microbiota for use in personalised medicine and other glycobiology applications.

The project will involve the use of ‘omics technologies and advanced bioinformatics techniques to identify novel CAZymes for biochemical and structural characterisation, whilst working closely with Ludger to prioritise target activities relevant for use in personalised medicine.

This exciting project will provide the student with extensive industrially relevant experience in glycoanalytics as well as expertise in the latest glycobiology, bioinformatics and structural techniques.

Informal enquiries may be made to

HOW TO APPLY 

Applications should be made by emailing with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Newcastle-Liverpool-Durham (NLD) BBSRC DTP Studentship Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

CASE studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries 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

1. Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown. Nat Commun (2020) 11:4017. doi: 10.1038/s41467-020-17847-5.
2. Complex N-glycan breakdown by gut Bacteroides involves an extensive enzymatic apparatus encoded by multiple co-regulated genetic loci. Nat Microbiol (2019) 4:1571-1581.
3. How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans. Proc. Natl. Acad. Sci. USA (2017) 114:7037-7042.
4. Structural basis for nutrient acquisition by dominant members of the human gut microbiota. Nature (2017) 541:407-411.
5. Glycan complexity dictates microbial resource allocation in the large intestine. Nat. Commun. (2015) 6:7481.
6. Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase. BMC Bioinformatics (2014) 15:196.
7. From Protein Structure to Function with Bioinformatics. 2nd edition. Springer, Dordrecht (2017).
8. Introducing endo-xylanase activity into an exo-acting arabinofuranosidase that targets side chains. Proc Natl Acad Sci USA. (2012) 109:6537-42.
9. The structure and function of an arabinan-specific alpha-1,2-arabinofuranosidase identified from screening the activities of bacterial GH43 glycoside hydrolases. J Biol Chem. (2011) 286:15483-95.


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