Illuminating mechanisms of RNA transcription by novel optical super-resolution imaging approaches, Biophysics or Biology – MPhil/PhD (Funded) Ref: 3307

About the award

Supervisors

Professor Christian Soeller, University of Exeter
Professor Steve West, University of Exeter

The University of Exeter’s College of Engineering, Mathematics and Physical Sciences in partnership with Bio-Techne, is inviting applications for a fully-funded PhD studentship to commence in April 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 £14,777 for 3.5 years full-time, or pro rata for part-time study.  The student would be based in the Living Systems Institute at the Streatham Campus in Exeter.

Optical super-resolution imaging has come to the forefront of biological research because it combines two critical advantages, (1) the specificity and contrast of fluorescence markers which has revolutionized biological imaging and (2) access to the spatial resolution range of 5-200 nm over which bio-molecular interactions occur and that traditional imaging techniques cannot capture. In this project, we will translate methods previously used for optical super-resolution in fixed cells into live cell preparations, supported by the chemical biology expertise of Bio-Techne, our partner in an academia-industry collaboration.

In addition to the focus on method development, where we will exploit reversibly binding markers to implement high-resolution live-cell super-resolution imaging, we will use these new approaches to observe mechanisms of RNA transcription – one of the most fundamental processes in Cell Biology.  Most transcription is carried out by RNA polymerase II (Pol II) but much of what we know about this comes from indirect experiments as we have been historically unable to directly observe the processes taking place.  One of our major research interests is the mechanism by which transcription terminates in a process essential for genome punctuation.  In utilizing our existing super-resolution expertise and developing new live cell capability, we aim to perform the first mechanistic dissection of the process by directly imaging it taking place.  In particular, we aim to test the current model that transcriptional termination is caused by a 5’-to-3’ exonuclease, Xrn2, pursuing a transcribing Pol II via the degradation of its associated nascent RNA.  In addition to its fundamental importance, many of the processes and factors implicated in termination are mis-regulated in diseases including cancer and neurodegenerative disorders.  This is an exciting opportunity at the interface of Biophysics and Molecular Biology underpinned by a strong commercial partner.

For this project we have partnered with Bio-Techne, a leading developer of high quality reagents and assay systems for biomedical researchers and clinical research laboratories. Bio-Techne Bristol is the home of the corporation’s chemical expertise and the manufacturing site for Tocris brand products. Bio-Techne will provide custom small molecule/peptide tools and fluorescent probes for this project, including development and synthesis of first-in-class compounds, which will enable the candidate to generate optical super-resolution data of outstanding quality. The candidate will have the opportunity to work closely with the industrial collaborator to gain additional commercial experience and transferable skills.

The project will be conducted in a collaboration between the Soeller and West laboratories which are based at the recently opened Living Systems Institute at the University of Exeter. The Living Systems Institute is a world-class, next generation, collaborative research community to revolutionize the diagnosis and treatment of diseases through basic research.

The ideal candidate has some experience in fluorescence imaging, quantitative analysis and basic biological techniques. The candidate will have a degree in Biophysics, Biology or a related area with a strong quantitative focus. We will provide training for all skills essential to this project including super-resolution imaging, molecular biology, data analysis and scientific writing. The successful candidate will have the opportunity to work in a highly interdisciplinary environment and interact with a highly motivated postgraduate cohort. The Living Systems Institute and the University of Exeter provide state-of-the-art facilities including super-resolution optical imaging, molecular biology, mass-spectrometry and high performance computing.
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 £14,777 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 3.5 years of full-time study to commence in April 2019 and is subject to confirmation of funding.

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 6.0  in 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)
• Names of two referees familiar with your academic work. You are not required to obtain references yourself. We will request references directly from your referees if you are shortlisted.
• 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 26 November 2018.  Interviews will be held on the University of Exeter Streatham Campus or by Skype the week commencing 3rd December 2018.
If you have any general enquiries about the application process please email stemm-pgr-admissions@exeter.ac.uk or phone +44 (0)1392 722730.  Project-specific queries should be directed to the main supervisor Prof Chreistian Soeller C.Soeller@exeter.ac.uk

Summary

Application deadline:26th November 2018
Value:£14,777 per year for 3.5 years
Duration of award:per year
Contact: PGR Admissions Office +44 (0)1392 722730 / 5150 stemm-pgr-admissions@exeter.ac.uk