About the Project
This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP) which is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bath, Bristol, Cardiff and Exeter, along with the Rothamsted Research Institute. The partnership has a strong track record in advancing knowledge through high quality research and teaching, in collaboration with industry and government.
Studentships are available for entry in September/October 2018.
All SWBio DTP projects will be supervised by an interdisciplinary team of academic staff and follow a structured 4-year PhD model, combining traditional project-focussed studies with a supporting but focussed taught first year with directed rotation projects.
Supervisory team:
Main supervisor: Dr Stefan Bagby (University of Bath)
Co-supervisors: Prof Frank Vollmer (University of Exeter) and Dr Paul Whitley (University of Bath)
The project exploits the first optical technique (plasmonically enhanced whispering gallery mode (WGM) microcavity sensor) capable of directly monitoring structural changes within individual biomolecules such as proteins for the study of ubiquitination, an important posttranslational modification involved in modulation and regulation of protein function in several cellular processes. Ubiquitination goes awry in numerous diseases. 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 involves the covalent attachment to a target protein (the “substrate”) of another small protein called ubiquitin (so called because it is found in almost all tissues of eukaryotic organisms). Ubiquitination can mark the substrate protein for proteasomal or autophagic degradation, or it can affect substrate function or location. Ubiquitin is covalently cross-linked to the substrate via formation of an isopeptide bond between its C-terminal carboxylate and the substrate’s N-terminal amine or ε-amino group of a substrate lysine residue.
In many cases a chain of ubiquitin molecules is assembled on a substrate protein. A ubiquitin monomer is linked to the chain via any one of its seven lysines or its 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 the biological outcome of ubiquitination, this project will provide detailed new insights into the links between E3 ligase function and resulting phenotype, and will therefore potentially advance understanding of the relationships between each E3 ligase and health and disease.
The project will involve a combination of cutting edge physical and biochemical methods to provide detailed new insights into ubiquitination, a key biochemical reaction that controls many cellular processes and occurs in most, if not all, eukaryotic cell types. Biochemical and chemical biology experiments including production of modified ubiquitin and enzymes (ligases and deubiquitinases), and in vitro ubiquitination assays, will be conducted at Bath (Bagby/Whitley), and single molecule WGM sensing studies of ubiquitin chain assembly will be conducted at Exeter (Vollmer).
Applicants must 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. In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in SWBio DTP projects, a minimum of a grade B in A-level Maths (or an equivalent qualification or experience) is required.
Candidates should apply using the University of Bath’s online application form selecting PhD programme in Biosciences (full-time) https://www.bath.ac.uk/study/pg/applications.pl#bio-sci./
For more information, please see: http://www.bath.ac.uk/science/postgraduate-study/research-programmes/funding/bbsrc-phds/
Funding Notes
BBSRC SWBio DTP studentships provide funding for a stipend (currently £14,553 per annum for 2017/18), research/training costs and UK/EU tuition fees for 4 years.
Applicants from the UK and EU, who have been resident is the UK for 3 years or more immediately prior to the start of their course, are eligible to apply for a full studentship. Applicants who are classed as International for tuition fee purposes are not eligible for funding.
For more information, please see: http://www.swbio.ac.uk/programme/eligibility/
Continue with Facebook
