About the Project
This project will be jointly supervised by Dr Adele Murrell (Department of Biology & Biochemistry, University of Bath) and Prof Dorothy Buck (Department of Mathematical Sciences, University of Bath)
The prospect for clinical gene editing to repair disease mutations, has been raised recently when the CRISPR/Cas9 technology was demonstrated to work in human embryos earlier this year . Aside from the ethical implications, gene editing can have unforeseen consequences on the expression of genes adjacent to the targeted gene. It is therefore important that we understand how these technologies can impact upon the three-dimensional (3D) structure of the DNA which is a major facilitator of orchestrated gene expression.
3D structure of chromatin: The DNA in our cells isn’t the stretched out, long, helical string depicted in text books. Rather, every DNA molecule is folded and packed into a highly structured, yet flexible scaffold, upon which the factors for gene expression assemble. The folding of DNA means that gene expression can occur in clusters and the expression of any given gene may affect that of its neighbour.
This project is will be to develop mathematical and bioinformatics based tools to explore the geometric principles governing the 3D structure of the genome from large-scale ‘omic’ data sets for human epigenetic profiles and state-of-the art imaging technologies. We will then examine the impact of targeted gene editing on the 3D genome structure.
The structured environment around the DNA is what defines epigenetic factors of gene expression. There is a growing public interest in epigenetics research and how epigenetics can explain the effects of life style choices on the DNA. There is also a strong public and health interest in how gene editing will affect genetic health. In the first instance the results of our study will form a platform that can be built upon to develop algorithms for predicting which regions of the genome can be safely and more precisely targeted by gene editing technologies. Data driven biology and systems approaches to biomedical sciences provide the means for large scale analysis of multiple cellular and biological features. The novelty of this project is that we will be among the first to use such data to understand how three dimensional structures affect the working of our genome.
Applicants should hold, or expect to receive, a First Class or good Upper Second Class Honours degree, or the equivalent from an overseas university, in a relevant subject, for example, Natural Sciences, Biology, Biochemistry or Mathematics. A master’s level qualification would also be advantageous.
Informal enquiries should be directed to Dr Adele Murrell ([Email Address Removed]) or Prof Dorothy Buck ([Email Address Removed])
Formal applications should be made via the University of Bath’s online application form for a PhD in Biology:
https://www.bath.ac.uk/samis/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-FP02&code2=0012
More information about applying for a PhD at Bath may be found here:
http://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/
Anticipated start date: 1 October 2018
Funding Notes
Some Research Council funding is available on a competition basis to Home and EU students who have been resident in the UK for 3 years prior to the start of the project. For more information on eligibility, see: https://www.epsrc.ac.uk/skills/students/help/eligibility/.
Funding will cover Home/EU tuition fees, a stipend (£14,553 per annum for 2017/18) and a training support fee of £1,000 per annum for 3.5 years. Early application is strongly recommended.
Applicants classed as Overseas for tuition fee purposes are NOT eligible for funding; however, we welcome all-year-round applications from self-funded candidates and candidates who can source their own funding.
References
Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions.
Stojic L, Niemczyk M, Orjalo A, Ito Y, Ruijter AE, Uribe-Lewis S, Joseph N, Weston S, Menon S, Odom DT, Rinn J, Gergely F, Murrell A.
Nat Commun. 2016 Feb 2;7:10406. doi: 10.1038/ncomms10406.
Topological aspects of DNA function and protein folding.
Stasiak A, Bates AD, Buck DE, Harris SA, Sumners de W.
Biochem Soc Trans. 2013 Apr;41(2):491-3. doi: 10.1042/BST20130006.
5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer.
Uribe-Lewis S, Stark R, Carroll T, Dunning MJ, Bachman M, Ito Y, Stojic L, Halim S, Vowler SL, Lynch AG, Delatte B, de Bony EJ, Colin L, Defrance M, Krueger F, Silva AL, Ten Hoopen R, Ibrahim AE, Fuks F, Murrell A.
Genome Biol. 2015 Apr 1;16:69. doi: 10.1186/s13059-015-0605-5
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