Effects of clustering and phosphorylation on nanoscale receptor signalling, BBSRC SWBio, PhD in Physics studentship (Funded) Ref: 3290

About the award

Supervisors

Lead Supervisor

Prof Christian Soeller, Chair in Physical Cell Biology, Department of Physics and Astronomy, University of Exeter

Additional Supervisors

Prof Derek Blake, Cardiff University

Prof Steffen Scholpp, Department of Biosciences, Collge of Life and Environmental Sciences, University of Exeter

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

The SWBio DTP is one of the 12 Doctoral Training Partnerships funded by the BBSRC to provide PhD training in areas of their strategic relevance.  The SWBio DTP is a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence.

The aim of this DTP is to produce highly motivated and excellently trained postgraduates in the BBSRC priority areas of Agriculture & Food Security (AFS) and World-Class Underpinning Bioscience (WCUB). These are growth areas of the biosciences and for which there will be considerable future demand.

The award:

There are over 30 (including up to 5 CASE studentships) fully-funded 4 year studentships* available to start in September 2019 across a wide range of biosicence academic disciplines. 

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP).  Up to 6 fully-funded studentships are being offered to start in September 2019 at the University of Exeter.

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. 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 cell function depends on clustering 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. 

For UK/EU nationals who meet the residency requirements outlined by the BBSRC, the studentship will cover funding for 4 years (48 months) as follows.  These awards might be available to part-time students, but only in exceptional circumstances.  It is recommended you speak to the lead supervisor prior to submitting an application.

•    a stipend at the standard Research Council UK rate; currently £14,777 per annum for 2018-2019
•    research and training costs
•    tuition fees (at the standard Research Councils UK rate)
•    additional funds to support fieldwork, conferences and a 3-month internship

Please refer to the regulations or Annex 1 of the Research Council Training Grant Guide to confirm that you meet the residence criteria for a fully-funded studentship.  Any further queries in relation to residency must be directed to the institution that you are applying to.

Entry requirements

Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology.  Applicants with a Lower Second Class degree will be considered if they also have Masters degree or have significant relevant non-academic experience.

In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification or experience is required.

If English is not your first language you will need to have achieved at least 6.5 in IELTS and no less than 6.5 in any section by the start of the project.  Alternative tests may be acceptable, please see  http://www.bristol.ac.uk/study/language-requirements/profile-c/.

Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award but no stipend.  Applicants who are classed as International for tuition fee purposes are not eligible for funding. 

Please refer to the regulations or Annex 1 of the Research Council Training Grant Guide to confirm that you meet the residence criteria for a fully-funded studentship.

The four universities have a very limited number of fully-funded 4 year studentships that EU nationals who do not meet the residency requirements would be eligible for.  Please contact us for for more information.

How to apply

Please be aware you will be asked to upload the following documents:

  • CV
  • Letter of application outlining your academic interests, prior research experience and reasons for wishing to undertake the project.  Please indicate your preferred project choice if applying for multiple BBSRC SWBio DTP projects.
  • Transcript(s) giving full details of subjects studied and grades/marks obtained.  This should be an interim transcript if you are still studying.
  • Two academic referees - see information below about references.
  • If you are not a national of a majority English-speaking country you will need to submit evidence of your proficiency in English (see entry requirements above)

The closing date for applications is midnight on Monday, 3 December 2018. Interviews will be held at the University of Exeter on 7 and 8 of February 2019.

Reference information
You will be asked to name 2 referees as part of the application process, however we will not expect receipt of references until the shortlisting stage. Your referees should not be from the prospective supervisory team.

If you are shortlisted for interview, please ensure that you two academic referees email their references to the pgrenquiries@exeter.ac.uk, 7 days prior to the interview dates.  Please note that we will not be contacting referees to request references, you must arrange for them to be submitted to us by the deadline.

References should be submitted by your referees to us directly in the form of a letter. Referees must email their references to us from their institutional email accounts. We cannot accept references from personal/private email accounts, unless it is a scanned document on institutional headed paper and signed by the referee.


If you have any general enquiries about the application process please email pgrenquiries@exeter.ac.uk.

Project-specific queries should be directed to the primary supervisor.

Selection process:

Please note, the studentship selection process will take place in two stages:

1.     The project supervisors will consider your application and may invite you to visit for an informal interview. You can apply for more than one BBSRC SWBio DTP project, although supervisors may take into account your interest and commitment to their particular project.  If you apply for multiple projects, please indicate your preferred project choice in your letter of application.  Each application for an individual project will be considered separately by the project supervisors.

2.     After closure of applications, each supervisory team will then nominate their preferred applicant.  A shortlist will be selected from these nominations and shortlisted applicants will be invited for interview on a selection day at the University of Bristol.  Please note that nomination by a project supervisor therefore does not guarantee the award of a studentship.

Data Protection
During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates.  These are not limited to, but may include disclosures to:

  •     the selection panel and/or management board or equivalent of the relevant programme,   
        which is likely to include staff from one or more other HEIs;
  •    administrative staff at one or more other HEIs participating in the relevant programme.

Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.

Summary

Application deadline:3rd December 2018
Value:Tuition fees and an annual stipend allowance at Research Council rates, currently £14,777 per year for 2018-19
Duration of award:per year
Contact: PGR Recruitment Office pgrenquiries@exeter.ac.uk