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Effects of clustering and phosphorylation on nanoscale receptor signalling. PhD in Bioscience (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 Christian Soeller, Department of Physics and Astronomy, College of Engineering, Maths & Physics; and also Living Systems Institute, University of Exeter

Additional Supervisors
- Professor Derek Blake, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University
- Dr Steffen Scholpp, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter
- Dr Yolanda Hill, Department of Mathematics, College of Engineering, Mathematics and Physical Sciences, University of Exeter
- Dr Joel Tabak-Sznajder, College of Medicine and Health
- Dr Vijay Rajagopal, Department of Biomedical Engineering, University of Melbourne

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

Programme Overview
The South West Biosciences Doctoral Training Partnership (SWBio DTP http://www.swbio.ac.uk/) is led by the University of Bristol, together with the Universities of Bath, Cardiff and Exeter, alongside Rothamsted Research.

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

Heart muscle cells contain a key receptor protein, the ryanodine receptor (RyR), which is an intracellular calcium channel. Muscle cell contraction is enabled by transient increases in cellular calcium levels, termed calcium transients, which result from calcium released through RyRs.

Recently it has been recognized that cell function can be greatly affected by modulation of receptor clustering. Receptor clustering refers to the close grouping of RyRs within intracellular membranes so that adjacent receptors are only few tens of nanometers apart. These groups come in many different sizes and contain between just a few to >100 receptors.

This project aims to improve our understanding how receptor clustering makes activation of these receptors more effective, and what happens if the clusters contain too few or too many receptors. To investigate this behaviour we will employ two microscopy techniques. The first technique is designed to accurately measure the clustering of proteins in intact cells, as well as their phosphorylation state. This requires imaging receptor distributions with molecular resolution which we have achieved with optical super-resolution imaging so that we can “see” individual biomolecules and count the number of RyRs in clusters (see also the image of RyR clusters in Fig. 1). The second technique uses calcium sensitive dyes imaged with a confocal microscope to directly see the calcium released through RyR clusters. By combining the two approaches we will determine how cluster size affects the amount and frequency of calcium being released through RyRs. In collaboration with colleagues in Cardiff we have identified a protein which modulates the clustering of RyRs. This protein, called myospryn, increases RyR clustering (i.e. causes more receptors to be within a closely packed group) when overexpressed. We will use this to modulate RyR clustering and observe how cell function, measured via monitoring the calcium released through RyRs, is altered.

To obtain insight how to predict cell function we will construct a mathematical model to allow us to predict the amount and frequency of calcium release resulting from any pattern of receptor clustering. The model will be based on a previously investigated simpler model that will be extended by using the new data generated here. Our insights could lead to novel treatment strategies aiming to rectify problems resulting from faulty receptor clustering.

The student will receive training in advanced fluorescence imaging, molecular biology, quantitative image analysis and mathematical modelling in the new interdisciplinary Living Systems Institute in Exeter.

Eligibility

To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria which is in line with UKRI guidelines 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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