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MRC DiMeN Doctoral Training Partnership: Mining the human gut microbiome for novel medically relevant glycoenzymes

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  • Full or part time
    Dr D Bolam
    Dr D J Rigden
    Dr J Marles-Wright
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Interested in studying how the human gut microbiota breaks down host glycans to use as nutrients and how this process can be exploited for medical applications?
Cell surface glycans play key roles in many signalling and recognition processes. Inter-individual variations in glycan composition are large, and these differences associate with disease risk, disease course and the response to therapy. Changes in glycosylation profile may potentially also be used as a marker for general metabolic health, e.g. to monitor healthy ageing.
A key part of the personalised medicine revolution is to be able to identify specific disease biomarkers quickly and accurately to enable the medication to be tailored to the patient. Glycan active enzymes (glycanases) are often used to identify and analyse discrete glycan structures as biomarkers (glycoprofiling), but there is a growing need for new enzyme activities to improve specificity for the structures targeted and provide enhanced biomarker detection.

This iCASE studentship is a collaboration between Dr David Bolam’s lab at Newcastle University Medical School, Dr Dan Rigden’s lab at Liverpool and Ludger Ltd (Oxford) to exploit the huge untapped resource of novel glycan active enzymes encoded by the human gut microbiota for use in glycoprofiling and other glycobiology applications.

The project will involve the identification and characterization of novel microbiota-derived glycanases, working with Ludger to identify the highest priority enzyme activities relevant for use in glycoprofiling. Genome mining and structural bioinformatics will be used to identify novel candidate enzymes in the Rigden lab. The student will then express selected enzymes and define their activity against a range of human glycan structures using the latest glycoanalytical techniques in the Bolam lab and at Ludger (e.g. UPLC-MS and HPAEC-PAD). Interesting enzyme targets will be advanced for structural studies to define the molecular basis for substrate specificity in the Marles-Wright lab at Newcastle, while at Ludger the student will receive extensive training in the area of medical glycoanalytics.

Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

iCASE Award: Industrial partnership project
Fully funded by the MRC for 3.5yrs, including a minimum of 3 months working within the industry partner. Enhanced stipend, tuition fees and budget for consumables, travel and subsistence.
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: https://goo.gl/8YfJf8
Good luck!

References

1. Cartmell et al. Proc. Natl. Acad. Sci. (2017) 114:7037-7042
2. Glenwright et al. Nature (2017) 541:407-411.
3. Rigden DJ (ed) From Protein Structure to Function with Bioinformatics. 2nd edition. Springer (2017)

How good is research at Newcastle University in Biological Sciences?

FTE Category A staff submitted: 30.60

Research output data provided by the Research Excellence Framework (REF)

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