Imperial College London Featured PhD Programmes
University of Edinburgh Featured PhD Programmes
University of Dundee Featured PhD Programmes
University of Southampton Featured PhD Programmes
University of East Anglia Featured PhD Programmes

Use of single molecule fluorescence and cryo-EM to study the regulation of RNA splicing


Project Description

One of the biggest challenges in molecular biology is presented by the selection of sites for RNA splicing. We cannot overstate its importance or apparent complexity. Splicing determines which mRNA and protein sequences a gene expresses. It is accurate, removing introns of 102-106 bases, but paradoxically flexible in mammals, where most genes produce multiple isoforms of mRNA. These may produce proteins with different functions (up to 1,800 functional isoforms of neurexin 3, for example) and switching is involved in memory, development, differentiation, signalling and disease. Numerous regulatory proteins and their binding sites have been identified by ensemble and ‘omic’ approaches, but our understanding of their mechanisms and functional integration remains very poor. We have recently made breakthrough findings by combining single molecule methods and chemical biology. These methods and a transformative vision of the dynamics of the process leave us poised to discover the mechanisms of selection.

This research is based on a multi-disciplinary group from the Universities of Leicester, Strathclyde and Glasgow. This group brings together expertise in nano-engineering, bio-organic chemistry, photonics, structural biology, RNA splicing and molecular biology, and has been funded by a BBSRC sLOLA grant for 5 years. The PhD project will fit into the heart of this consortium. It will involve the analysis of splicing regulatory proteins, fitted with fluorescent tags, and their association with pre-mRNA and with other proteins in individual complexes. In addition, it will involve developing novel methods for analysing complexes using cryo-electron microscopy. These approaches hold the possibility of making major advances in our understanding.

The University if Leicester is very well equipped for this research. We have several home-built single molecules microscopes, which we have been using for studying splicing for some years, and we have a relatively new and already highly productive cryo-electron microscope.

Eligibility:

UK/EU applicants only.

Entry requirements:

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject.

The University of Leicester English language requirements apply where applicable: https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

How to apply:

Please refer carefully to the application guidance and apply using the online application link at: https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

Project / Funding Enquiries:
Application enquiries to
Closing date for applications: Sunday 12th January 2020

Funding Notes

4 year MIBTP studentship offering

Stipend at UKRI rates

Tuition fees at UK/EU rates

References

Jobbins, A.M., Reichenbach, L.F., Lucas, C.M., Hudson, A.J., Burley, G.A., & Eperon, I.C.* (2018). The mechanisms of a mammalian splicing enhancer. Nucleic Acids Research 46, 2145-2158 (doi: 10.1093/nar/gky056). Breakthrough article.

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2019
All rights reserved.