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MRC DiMeN Doctoral Training Partnership: Epigenetic maintenance in normal and malignant haematopoietic stem cells


   MRC DiMeN Doctoral Training Partnership

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  Prof Dawn Coverley, Dr D G Kent  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

York United Kingdom Bioinformatics Cancer Biology Cell Biology Developmental Biology Genetics Genomics Human Genetics Molecular Biology Molecular Genetics

About the Project

The process by which stem cell populations are established and maintained is highly relevant to understanding ageing, degenerative diseases and cancer. In the blood system, age-related clonal haematopoiesis in otherwise healthy individuals is an indicator of early disease development and linked with mutations in epigenetic modifiers. Recently we showed that a protein called Cip1-interacting Zinc finger protein 1 (CIZ1) protects against haematological malignancies in mice, and influences the stability of at least three different histone post-translational modifications (PTMs), making it a candidate epigenetic modifier with possible function in hematopoietic stem cells (HSCs) and disease avoidance.

This project will establish the role of CIZ1 in primary HSCs making use of existing genetically modified mice, and derived cell populations, and drawing on the expertise of two supervisors specialising in CIZ1 or HSC biology. The project will involve flow cytometry for isolating and characterising blood cell populations, and will use a wide range of single cell molecular assays (e.g., single cell RNA-sequencing, single cell ATAC-sequencing), functional and in vitro transplantation assays, as well as population analysis using well established cell biology techniques.

https://pure.york.ac.uk/portal/en/researchers/dawn-alison-coverley(fe30002c-0f4f-4063-9496-ef338ff4bcc5)/profile.html

https://pure.york.ac.uk/portal/en/researchers/david-geoffrey-kent(e157ec5d-174b-4b66-96fe-3eb446c84ba0).html

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

http://www.dimen.org.uk/how-to-apply/application-overview


Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover UK tuition fees, stipend and project costs as standard. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will be awarded to exceptional candidates only, due to the competitive nature of this scheme. Please read additional guidance here: http://www.dimen.org.uk/how-to-apply/eligibility-funding
Studentships commence: 1st October 2022
Good luck!

References

1. Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture. Stewart ER, Turner RML, Newling K, Ridings-Figueroa R, Scott V, Ashton PD, Ainscough JFX, Coverley D. Nat Commun. 2019 Jan 28;10(1):460. doi: 10.1038/s41467-018-08072-2. PMID: 30692537
2. The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory. Ridings-Figueroa R, Stewart ER, Nesterova TB, Coker H, Pintacuda G, Godwin J, Wilson R, Haslam A, Lilley F, Ruigrok R, Bageghni SA, Albadrani G, Mansfield W, Roulson JA, Brockdorff N, Ainscough JFX, Coverley D. Genes Dev. 2017 May 1;31(9):876-888. doi: 10.1101/gad.295907.117. Epub 2017 May 25. PMID: 28546514 Free PMC article.
3. Population dynamics of normal human blood inferred from somatic mutations. Lee-Six H, Øbro NF, Shepherd MS, Grossmann S, Dawson K, Belmonte M, Osborne RJ, Huntly BJP, Martincorena I, Anderson E, O'Neill L, Stratton MR, Laurenti E, *Green AR, *Kent DG, *Campbell PJ. Nature. 2018 Sep;561(7724):473-478.
4. Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal. *Shepherd MS, *Li J, Wilson NK, Oedekoven CA, Li J, Belmonte M, Fink J, Prick JCM, Pask DC, Hamilton TL, Loeffler D, Rao A, Schröder T, Göttgens B, *Green AR, *Kent DG. BLOOD. 2018 Aug 23;132(8):791-803.
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