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Ribonucleic acid folded structure probed using ion beams


   Department of Chemistry

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  Prof Frederick Currell, Prof J Micklefield, Prof J Waltho, Dr A Baidak  Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

The major challenge of structural biology is determining 3D folded RNA structures [1,2]. This project plans to develop an innovative way to determine these structures. Whilst a small amount of our RNA codes for proteins, much more acts to choreograph the molecular processes of life so determining the 3D folded structures RNA takes-up is a key requirement for furthering our understanding of the processes of life [3].

We will use the fast helium ions, uniquely available in the UK at the Dalton Cumbrian Facility (DCF) [4]. These ions produce gimlet-like damage on the sub-nanometre scale, which can effectively dissect folded RNA. Near-by parts of the folded RNA are more likely to fragment together as a single ion passes through the RNA structure. Hence fragments which occur more commonly indicate parts of the folded structure which are close together.

 The student will develop a new procedure to exploit this phenomenon by:

1) irradiating simple RNA structures and analysing the fragmentation to determine the best chemical conditions,

2) optimising and determining the efficiency of putting poly-A tails on to ion-damaged ends as a prerequisite for next-gen sequencing,

3) perfecting magnetic bead-fishing to remove separate off the end-fragments which do not contain the same proximity information,

4) combining the steps 1-3 above with next-gen sequencing to produce data from which proximity maps and the folded structure can be deduced. This process will be repeated for increasingly complex structures, starting with the Add1-aptamer and the RNA puzzles collection, and

5) developing analytical techniques to take the sequencing data and transform it into a map of the proximity of different parts of the RNA.

 The student working on this project will have the opportunity to work within an internationally leading, multidisciplinary collaborative team and will have the chance to contribute to a major break-through in structural biology.

Academic background of candidates 

Applicants are expected to hold, or about to obtain, a minimum upper second-class undergraduate degree (or equivalent) in Physics, Chemistry, Biochemistry or a related discipline. A Masters degree in a relevant subject and/or experience and of these disciplines is desirable. Due to the transdisciplinary nature of this project, aptitude for independent learning of new skills is an essential pre-requisite. 

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. We know that diversity strengthens our research community, leading to enhanced research creativity, productivity and quality, and societal and economic impact. We actively encourage applicants from diverse career paths and backgrounds and from all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status.

All appointments are made on merit.

Contact for further Information

Professor Fred Currell, [Email Address Removed], https://www.researchgate.net/profile/Fred-Currell-2, https://www.research.manchester.ac.uk/portal/frederick.currell.html


Funding Notes

This is a 3.5 year EPSRC DTG studentship. Funding will cover UK tuition fee and stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
Start date: September 2022

References

[1] Richardson et al 2019 Biochemistry doi: 10.1021/acs.biochem.9b0053
[2] Kim et al 2020 Nat. Com. doi 10.1038/s41467-019-13942-4
[3] Masayuki and Corey 2016 Nat. Rev. Drug Discovery doi 10.1038/nrd.2016.117
[4] Leay et al 10.3390/app112311081

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