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An exploration of the links between mitochondrial function and splicing regulation. PhD in Medical Studies (SWBio DTP)

  • Full or part time
  • Application Deadline
    Monday, December 02, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Lead Supervisor
Professor Lorna Harries, College of Medicine and Health, University of Exeter

Additional Supervisors
- Professor Mark Lindsay, Department of Pharmacy and Pharmacology, University of Bath
- Dr Nicola Jeffery, College of Medicine and Health, University of Exeter

Location: University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW

Programme Overview
The South West Biosciences Doctoral Training Partnership (SWBio DTP) is led by the University of Bristol, together with the Universities of Bath, Cardiff and Exeter, alongside Rothamsted Research. This partnership also includes the following collaborative partners; Marine Biological Association (MBA), Plymouth Marine Laboratory (PML), Swansea University, UCB Pharma, University of the West of England (UWE) and SETsquared Bristol.

These institutions represent a distinctive group of bioscience research staff and students, with established international, national and regional networks, and widely recognised research excellence. As research leaders, we have a strong track record in advancing knowledge through high-quality research and teaching, in partnership with industry and the government.

For more information about the programme structure, please visit https://www.swbio.ac.uk/programme/

Funding for 2020/21
These studentships are available to UK and EU nationals who have established UK residency (EU nationals must have ordinarily lived in the UK throughout the three years preceding the start of the studentship).

The four core universities (Bath, Bristol, Cardiff and Exeter) have a very limited number of fully-funded four year studentships for EU students who do not meet the residency requirements (1-2 studentships per university)*. Please contact the relevant university for more information.

*These are not available for CASE DTP studentships or Standard DTP studentships with a collaborative partner

Project Description
Alternative splicing (the ability of cells to make multiple types of RNA messages from a single gene) and problems with the function of mitochondria are both frequently found in connection with important human diseases, but the links between them are not clear. It may be that disruption of mitochondrial function causes disruption of patterns of alternative splicing, the converse may be true, or a combination of both. There is not much known about the links between the two processes, but a better understanding of how one impacts the other may lead to new treatments for disease.

In this project the student will unravel the basis of this association by looking to see whether changes in patterns of alternative splicing are produced in specifically in response to low doses of chemicals which damage mitochondria. Changes to how splicing is regulated arising from this treatment and the precise effects of this on the portfolio of RNA messages made by the cell will then be determined by measuring the entire RNA output from the cell, followed by mathematical means of turning those data from a list of interesting genes to a network, which will identify which are the important genes causing changes in function. Secondly, the student will look to see if disrupting patterns of normal alternative splicing results in mitochondrial damage. We will target the agents that bring about splicing regulation and then look to see if there are changes in how well the mitochondria process glucose to make ATP, or whether there are changes to their morphology or their viability. Finally, genes at the interface of mitochondrial function and alternative splicing identified through our mathematical analysis will be manipulated in vitro to determine whether it is possible to guard the cells against mitochondrial damage by manipulating splicing patterns, or to safeguard the splicing patterns of the cell by attenuating mitochondrial function.

Eligibility
To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria in line with UKRI guidelines. Please see the following webpage for further details https://www.swbio.ac.uk/programme/eligibility/.

A fully-funded four year SWBio DTP studentship will cover:

• a stipend* at the standard UKRI rate; currently £15,009 per annum for 2019-2020
• research and training costs
• tuition fees (at the standard UKRI rate)
• additional funds to support fieldwork, conferences and a 3-month internship

Funding Notes

SWBio DTP funded studentship available for September 2020 entry. The studentship will provide funding of fees and a stipend which is currently £15,009 per annum for 2019-20, on a full time basis.

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