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MRC DiMeN Doctoral Training Partnership: Using bioinformatics to identify pathways regulating pancreatic beta-cell function and survival


Project Description

Applications are invited for a PhD studentship under the supervision of Dr Catherine Arden (Newcastle University), Dr Adrian Teo (A*STAR Singapore) and Professor Penny Lovat (Newcastle University). This PhD will give the unique opportunity to study with world-leading scientists both in the UK and in Singapore.

The project will explore the impact of obesity on nutrient sensing mechanisms in pancreatic beta-cells. These cells are particularly sensitive to changes in nutrient availability, both in their ability to release insulin in response to acute nutrient stimulation but also in their predisposition to dysfunction and demise in response to chronic exposure to excess circulating nutrients. We believe that changes in the autophagosomal/lysosomal pathways are critical in this process. Understanding the pathways mediating beta-cell impairment is essential to understand how type 2 diabetes develops and to identify targets for pharmacological manipulation. During this PhD, the student will explore the impact of nutrients on human pancreatic beta-cell autophagy, survival and function using novel and innovative methodology including mRNA-seq and bioinformatics, alongside other wet laboratory techniques. The aim will be to identify proteins that are altered by nutrient availability. Identification of these targets in human tissue with correlation with clinical data and post-transplant outcomes will allow for direct extrapolation to human disease.

The successful candidate will join a team of experts in beta-cell physiology, autophagy and human beta-cell development in a multi-collaborative project between Newcastle University and A*STAR Singapore. The student will receive extensive training in mRNA-seq and bioinformatics (with support from in-house facilities), as well as cell culture, immunohistochemistry and molecular biology. Primarily based at Newcastle University, the studentship will include a 1 year placement at the Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore. The cross-site nature of the studentship will provide an innovative training environment and offer the student access to courses / training at both Universities.

The ideal candidate will have a strong background and interest in human cell biology. They will hold a first class or upper second class (or non-UK equivalent) Bachelor’s degree or a Master’s degree in a relevant subject such as biological sciences or molecular biology, and be experienced in some experimental work relevant to the project themes. We seek a highly self-motivated, well organised and committed candidate to tackle the significant challenges of this project who is also able to communicate their results and ideas effectively.

For further information please see supervisor webpages.
Catherine Arden (http://www.ncl.ac.uk/icm/people/profile/catherinearden)
Adrian Teo (https://www.a-star.edu.sg/imcb/Science/Investigators/Independent-Fellows/Independent-Fellows-Profile/ResearchListID/81)
Penny Lovat (http://www.ncl.ac.uk/icm/people/profile/pennylovat)

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

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
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: View Website
Good luck.

References

Zummo FP, Cullen KS, Honkanen-Scott M, Shaw JAM, Lovat PE, Arden C. Glucagon-Like Peptide 1 Protects Pancreatic β-Cells From Death by Increasing Autophagic Flux and Restoring Lysosomal Function. Diabetes 66:1272-1285, 2017.

Teo, K.K.A.*, Lim, C.S., Cheow, L.F., Kin, T., Shapiro, J.A., Kang, N.-Y., Burkholder, W., and Lau, H.H. Single cell analyses of human islet cells reveal de-differentiation signatures. Cell Death Discovery 4:14, 2018. *Corresponding author

Hernandez-Tiedra S, Fabrias G, Davila D, Salanueva IJ, Casas J, Montes LR, Anton Z, Taboda EG, Slazar M, Lorente M, Nylandsted J, Armstrong JL, Lopez-Valero V, McKee CS, Puebla AS, Lopez RG, Martinez JG, Abad JL, Hanada K, Boya P, Goni FM, Guzman M, Lovat PE, Jaattela M, Alonso A, Velasco G. Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilisation. Autophagy 12:2213-2229, 2016.

How good is research at Newcastle University in Clinical Medicine?

FTE Category A staff submitted: 147.13

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

Click here to see the results for all UK universities

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