Effects of clustering and phosphorylation on nanoscale receptor signalling. PhD in Bioscience (SWBio DTP) Ref: 3720
About the award
Professor Christian Soeller, Department of Physics and Astronomy, College of Engineering, Maths & Physics; and also Living Systems Institute, University of Exeter
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
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.
The programme particularly aims to provide students with outstanding interdisciplinary research training within the following themes:
- Advancing the frontiers of bioscience discovery
- Bioscience for sustainable agriculture and food
- Bioscience for an integrated understanding of health
Importantly this research training is also underpinned by transformative technologies, allowing you to expand the boundaries of your research through innovative tools, technologies and approaches.
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
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.
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
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.
For more informaton about entry requirements please visit https://swbio.ac.uk/programme/eligibility/
Equality, Diversity and Inclusion Statement
We want to support diverse and inclusive work environments. We therefore welcome applications from individuals regardless of their race, ethnicity, sexual orientation, religion, age, gender, or disability status. We welcome applications from individuals who have previously studied at any recognised Higher Education Institute and from a range of career paths (please refer to the SWBio DTP academic criteria for eligibility), including individuals who have previously trained in the sciences and are wanting to return to scientific research.
We particularly encourage applications from BAME* and mature (this is classed as 30+ years) individuals as these backgrounds are currently underrepresented within our student cohort.
*Black, Asian and minority ethnic.
How to apply
Please be aware you will be asked to upload the following documents:
- Curriculum Vitae (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 SWBio DTP projects.
- Transcript / degree certificates(s). This should be an interim transcript if you are still studying.
- Two academic referees - see information below about references.
- English language certificates (where applicable )
The closing date for applications is midnight on Monday, 2 December 2019. Interviews will be held at the University of Exeter in the weeks commencing 27 January 2020 and 3 February 2020.
You will be asked to name 2 referees as part of the application process, however we will not expect receipt of references until after the shortlisting stage. Your referees should not be from the prospective supervisory team.
If you are shortlisted for interview, please ensure that your two academic referees email their references to the firstname.lastname@example.org, 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 email@example.com.
Project-specific queries should be directed to the primary supervisor.
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 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.
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.
|Application deadline:||2nd December 2019|
|Value:||Tuition fees and an annual stipend allowance at Research Council rates, currently £15,009 per year for 2019-20|
|Duration of award:||per year|
|Contact: PGR Recruitment Officefirstname.lastname@example.org|