University of Exeter funding: The structural dynamics of botulinu

The structural dynamics of botulinum neurotoxins, Biosciences – PhD (Funded) Ref: 3585

About the award

Supervisors

Dr JJ Phillips
Professor Frank Vollmer

Location:

Living Systems Institute, Streatham Campus, Exeter

The University of Exeter’s College of Life and Environmental Sciences, in partnership with Ipsen, is inviting applications for a fully-funded PhD studentship to commence in September 2019 or as soon as possible thereafter.  For eligible students the studentship will cover UK/EU tuition fees plus an annual tax-free stipend of at least £17,009 for 4 years full-time, or pro rata for part-time study.  The student would be based in The Living Systems Institute in the College of Life and Environmental Sciences at the Streatham Campus in Exeter.

Project Description:
Clostridium botulinum toxins (BoNTs) are the most toxic substances known to mankind and exposure can cause fatal neuromuscular paralysis (botulism). However, given at a suitable dose, BoNTs are highly effective medicines for a diverse range of diseases, including spasticity and musculoskeletal conditions. BoNTs are large, multi-functional proteins that must achieve endocytosis into the motor neuron, release into the cytosol, binding to and enzymatic digestion of substrate, ultimately blocking neurotransmission. These functions are dependent on dynamic changes in its structure that relate to protein stability, a key property for biopharmaceuticals. This project will investigate the linkage between the enzyme dynamics, bio/medical function and drug stability. The aims are to (i) understand the molecular mechanisms of infection, (ii) support the safe and effective development of BoNT therapeutics and (iii) differentiate modes of action of different BoNT serotypes.
This project is an opportunity to develop and apply advanced biophysical methods to determine the structural dynamics and stability of large proteins – including hydrogen/deuterium-exchange mass spectrometry, single-molecule optical spectroscopy and protein structural modelling. This studentship provides an exciting opportunity to study the structure and dynamics of botulinum toxins relating to both Clostridium botulinum neurotoxicity and to the development of next generation therapeutics.

[1] M. Kish, et al., bioRxiv.org 2019, 10.1101/654665
[2] E. Kim et al., Vollmer, Science Advances 2017, 3, e1603044
[3] C. L. Dobson et al., Scientific Reports 2016, 6, 38644.
[4] T. Klein et al., Nature Communications 2015, 6, 7877.

This award provides annual funding to cover UK/EU tuition fees and a tax-free stipend.  For students who pay UK/EU tuition fees the award will cover the tuition fees in full, plus at least £17,009 per year tax-free stipend.  Students who pay international tuition fees are eligible to apply, but should note that the award will only provide payment for part of the international tuition fee and no stipend. 

The studentship will be awarded on the basis of merit for 4 years of full-time study to commence in September 2019.

Entry requirements

Applicants for this studentship 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. 

If English is not your first language you will need to have achieved at least 6.5  IELTS and no less than 6.0 in any section by the start of the project.  Alternative tests may be acceptable (see http://www.exeter.ac.uk/postgraduate/apply/english/).

How to apply

In the application process you will be asked to upload several documents. 
• CV
• Letter of application (outlining your academic interests, prior research experience and reasons for wishing to undertake the project).
• Transcript(s) giving full details of subjects studied and grades/marks obtained (this should be an interim transcript if you are still studying).
• Two references from referees familiar with your academic work. If your referees prefer, they can email the reference direct to stemm-pgr-admissions@exeter.ac.uk quoting the studentship reference number.
• If you are not a national of a majority English-speaking country you will need to submit evidence of your proficiency in English.

The closing date for applications is midnight on 23rd August 2019.  Interviews will be held on the University of Exeter Streatham Campus on 2nd September 2019.

If you have any general enquiries about the application process please email stemm-pgr-admissions@exeter.ac.uk or phone +44 (0)1392 722730 or +44 (0)1392 725150.  Project-specific queries should be directed to the main supervisor (jj.phillips@exeter.ac.uk).

Summary

Application deadline:23rd August 2019
Value:£15,009 per year for 4 years
Duration of award:per year
Contact: PGR Admissions Office +44 (0)1392 722730 / 5150 stemm-pgr-admissions@exeter.ac.uk