Enzyme mechanisms studied by single molecule optical sensing. PhD in Physics and Astronomy SWBio DTP) Ref: 3723
About the award
Professor Frank Vollmer, Department of Physics and Astronomy, College of Engineering, Mathematics and Physical Sciences, University of Exeter
Dr Stefan Bagby, Department of Biology and Biochemistry, University of Bath
Professor Janet Anders, Department of Physics and Astronomy, College of Engineering, Maths and Physical Sciences, University of Exeter
Dr Paul Whitley, Department of Biology and Biochemistry, University of Bath
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
Ubiquitination is an important post-translational modification involved in modulation and regulation of protein function in many processes in most, if not all, eukaryotic cell types; ubiquitination goes awry in numerous diseases. Ubiquitination involves the covalent attachment to a target protein (the “substrate”) of one molecule, or multiple molecules in chains, of a small protein called ubiquitin (Figure 1). As described below, different types of ubiquitin chains can be assembled; this is important because chain type determines the biological outcome of ubiquitination (e.g. whether the substrate protein is degraded, or its function or location is affected), but currently it is difficult to determine chain type. The aim is to develop a rapid, accurate and user-friendly method to identify the type of ubiquitin chain assembled by any E3 ubiquitin ligase, at the same time providing new insights into ubiquitination mechanism and kinetics.
Ubiquitination, catalysed by ubiquitin ligases, involves covalent conjugation of ubiquitin to the protein substrate via formation of an isopeptide bond between ubiquitin’s C-terminal carboxylate and the substrate’s N-terminal amine or amino group of a lysine residue. In many cases a chain of ubiquitin molecules is assembled on a substrate protein (Figure 1) whereby a ubiquitin monomer is linked to the chain via any one of seven lysines or N-terminus. Ubiquitin chains can involve a single type of lysine linkage or mixed linkages, with each linkage producing a different degree of flexibility and repertoire of conformational states. Since chain type determines biological outcome, this project will provide detailed new insights into the relationships between E3 ligase function and resulting phenotype, and will therefore potentially advance understanding of the relationships between particular ubiquitin ligases and health and disease.
The project will involve a combination of cutting edge physical and biochemical methods. Ubiquitination reactions will be studied using plasmonically enhanced whispering gallery mode (WGM) microcavity sensing (Figure 1). This is the first optical technique capable of directly monitoring structural changes within individual biomolecules such as proteins. A major aim will be establishing whether each type of ubiquitin linkage has a unique WGM signature. Biochemical and chemical biology experiments with Drs Bagby and Whitley at Bath will include ubiquitination assays, and production of ubiquitin and enzymes (ligases and deubiquitinases) modified for immobilisation on gold nanoparticles that are used in WGM sensing. Single molecule WGM sensing studies of ubiquitin chain assembly will be conducted at Exeter with Professor Vollmer’s group.
To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria 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 Research Council UK rate; currently £15,009 per annum for 2019-2020
• research and training costs
• tuition fees (at the standard Research Councils UK 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 certificate(s). This should be an interim transcript if you are still studying.
- Two academic referees - see information below about references.
- English language certificate (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 email@example.com, 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 firstname.lastname@example.org.
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 Officeemail@example.com|