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Regulation of membrane contact sites in mammalian cells. PhD in Biosciences (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
Dr Joseph Costello, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter

Additional Supervisors
- Dr Julien Licchesi, Department of Biology and Biochemistry, University of Bath
- Professor Michael Schrader, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter

Location: University of Exeter, Streatham Campus, Exeter, EX4 4QJ

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
The cell contains numerous, distinct organelles which are specialised to carry out a particular role but are also part of wider networks or production lines which requires cooperation with other organelles. For example, certain
lipids are often partly metabolised in one organelle, such as peroxisomes or mitochondria, before being transferred to another such as the endoplasmic reticulum for further processing. This type of communication is required for energy generation, the production of lipids required to build nerve cell membranes, and activation of the cells recycling systems.

The idea that organelles need to come together to communicate and collaborate is an exciting new field and
we still know relatively little about how this works. Its importance was recently underlined by studies which
observed alterations in organelle interactions in diseases such as Alzheimer’s, Parkinson’s and metabolic disorders. Disrupted organelle interactions have also been implicated in the ageing process and an emerging concept is the idea that organelle interactions impacts on reactive oxygen species (ROS) signalling and homeostasis.

Recent research revealed that organelles interact at membrane contact sites, points where apposing organelle
membranes are in close proximity allowing metabolite and signal exchange. Contact sites can be formed when
proteins on different organelle membranes interact and numerous “tethering” complexes have now been identified for different organelles. In this emerging and dynamic the next wave of research will focus on how membrane contact sites are regulated and how their dysfunction is linked to disease, which is currently unknown. A long term aim is to pursue the modulation of organelle contact sites as a potential therapeutic approach.

In this project, the student will investigate how interaction between three organelles, the endoplasmic reticulum,
peroxisomes and mitochondria is regulated in mammalian cells. This will build on preliminary evidence that posttranslational modification of contact site proteins, which control organelle interactions, regulates their tethering function.

They will receive training in mammalian cell culture, advanced microscopy techniques (using novel fluorescent reporters and electron microscopy) as well as in protein characterisation techniques including coimmunoprecipitation, protein purification and ubiquitination assays.

This project will benefit from the expertise of the two supervisors in both organelle contact site and ubiquitin
biology and from the cutting-edge and supportive research environments at the Universities of Exeter and Bath. This 5 / 13 will allow the student to receive excellent training and be equipped with all the essential skills to become a successful future scientist.

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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