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Deciphering a novel anti-ageing epigenetic programme


   Faculty of Biology, Medicine and Health


Manchester United Kingdom Biochemistry Bioinformatics Cancer Biology Cell Biology Genetics Molecular Biology

About the Project

Over two decades of intense research in the field of epigenetics have produced compelling evidence that chromatin modifications are crucial for processes such as DNA repair, transcription, splicing, mitosis, meiosis, and in the preservation of the epigenetic memory of cells. One of the best examples of a chromatin modification implicated in that sort of repertoire of functions is methylation at histone 3 on lysine 4 (H3K4).

This abundant and conserved modification is deposited through a complex called the MLL/SET/COMPASS complex comprising a core complex and Histone MethylTransferase (HMTs) enzymes. Interestingly, lowering the levels of methyl marks at H3K4 using RNAi directed at the core complex increases C. elegans lifespan, but eradicating H3K4 methylation shortens lifespan.

Using ChIP-seq and RNA-seq, we have identified a number of targets that could underscore a new epigenetic programme essential to prevent ageing or promote longevity.

Your project will aim at characterising this epigenetic programme using RNAi, transgenesis, CRISPR, and next generation sequencing technologies such as RNA-seq, ChIP-seq, and ATAC-seq. At the end of your PhD, you will have developed an expertise for both wet lab and bio-informatics using R and Python programming language.

Training/techniques to be provided:

The candidate will have the opportunity to learn a broad range of techniques such as genetics, cell culture, and big data analysis using R and Python as programming language from two laboratories (Poulin and Sharrocks). You will also perform genome editing using CRISPR to engineer new C. elegans strains as well as manipulate the genome of Embryonic Stem Cells. You will have access to core facilities for next generation sequencing as well as state-of-the-art microscopy.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject of Biochemistry, Molecular Biology, or Genetics. Candidates with experience in bio-informatics or with an interest in epigenetics and sequencing technology are encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website).

References

Sfakianos AP, Mellor LE, Pang YF, Kritsiligkou P, Needs H, Abou-Hamdan H, Désaubry L, Poulin GB, Ashe MP, Whitmarsh AJ; The mTOR-S6 kinase pathway promotes stress granule assembly; Cell Death Differ. 2018 Nov;25(10):1766-1780.

Yang SH, Andrabi M, Biss R, Murtuza Baker S, Iqbal M, Sharrocks AD; ZIC3 Controls the Transition from Naive to Primed Pluripotency; Cell Rep. 2019 Jun 11;27(11):3215-3227

Monagan RM, Barnes RG, Fisher K, Andreou T, Rooney N, Poulin GB, Whitmarsh AJ; A nuclear role for the respiratory enzyme CLK-1 in regulating mitochondrial stress responses and longevity; Nat Cell Biol. 2015 Jun;17(6):782-92

Han S, Schroeder EA, Silva-García CG, Hebestreit K, Mair WB, Brunet A. Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan. Nature. 2017 Apr 13;544(7649):185-190

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