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Molecular mechanisms of epigenetic reprogramming

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  • Full or part time
    Dr P Hajkova
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Development of any organism starts with a totipotent cell (zygote). Through series of cell divisions and differentiation processes this cell will give rise to the whole organism containing hundreds of specialised cells. While the cells at the onset of development have the capacity to generate all cell types (ie are toti-or pluripotent), this developmental capacity is progressively lost as the cells undertake cell fate decisions.
At the molecular level, the memory of these events is laid down in a complex layer of epigenetic modifications at both the DNA and the chromatin level. Unidirectional character of the developmental progress dictates that the key acquired epigenetic modifications are stable and inherited through subsequent cell divisions. This paradigm is, however, challenged during cellular reprogramming that requires de-differentiation (nuclear transfer, induced pluripotent stem cells, wound healing and regeneration in lower organisms) or a change in cell fate (transdifferentiation).

The main research focus of our laboratory is trying to understand molecular processes that underlie global erasure of epigenetic information. As in vitro cellular reprogramming systems are notoriously inefficient, we focus on the epigenetic reprogramming events that occur naturally in vivo during mouse development (in the mouse zygote and in the early mouse germ cells). We are particularly interested in 1) the erasure and dynamics of DNA modifications during these processes and 2) the chromatin assembly/disassembly and underlying histone dynamics.

The project combines the use of mouse developmental model, state-of-the-art mass spectrometry (LC/MS) and biochemical approaches and hence provide ideal opportunity to learn wide range of methods while working in an exciting and competitive research field.

For more information, please contact Petra Hajkova ([Email Address Removed])

Funding Notes

This project is competition funded for students worldwide.

If successful the student would receive full tuition fee payment for 3.5 years as well as a tax free stipend amounting to £21,000pa paid in monthly instalments for the duration of their studentship.

Whilst Overseas Students are eligible, funding is more limited so only exceptional OS students will be considered.


Hill PWS, Leitch HG, Requena C, Sun Z, Amouroux R, Trufero M, Borkowska G, Terragni J, Vaisvila R, Linnett S, Dharmalingham G, Haberle V, Lenhard B, Zheng Y, Pradhan S, Hajkova P: Germline epigenetic reprogramming enables primordial germ cell-to-gonocyte transition in mouse. Nature, 2018 Mar 15;555(7696):392-396. doi: 10.1038/nature25964. Epub 2018 Mar 7

Leitch HG, Hajkova P. :Eggs sense high fat diet. Nat Genet. 2018 Mar;50(3):318-319. doi: 10.1038/s41588-018-0068-1

Rošić S*, Amouroux R*, Requena C*, Linnett S, Selkirk ME, Emperle M, Jeltsch A, Schiffer PH, Bancroft A, Grencis R, Hajkova P+ and Sarkies P+: Evolutionary analysis reveals DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity. Nat Genet. 2018 Mar;50(3):452-459. doi: 10.1038/s41588-018-0061-8. Epub 2018 Feb 19 (+ senior co-authors).

Amouroux, R., Nashun, B., Shirane, K., Nakagawa, S., Hill, P. W. S., D'Souza, Z., Nakayama M, Matsuda M, Turp A, Ndjetehe E, Encheva V, Kudo N, Koseki H, Sasaki H and. Hajkova, P. : De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nat Cell Biol, 2016 18(2), 225

Nashun B., Hill P.W.S., Smallwood S.A., Dharmalingam G., Amouroux R., Clark S.J., Sharma V., Ndjetehe E, Pelczar P, Festenstein R, Kelsey G and Hajkova P.: Continuous Histone Replacement by Hira Is Essential for Normal Transcriptional Regulation and De Novo DNA Methylation during Mouse Oogenesis. Mol Cell 2015, 60(4), 611-625.

Nashun B, Hill PW, Hajkova P.: Reprogramming of cell fate: epigenetic memory and the erasure of memories past. EMBO J. 2015 May 12;34(10):1296-308.

Leitch HG, McEwen KR, Turp A, Encheva V, Carroll T, Grabole N, Mansfield W, Nashun B, Knezovich JG, Smith A, Surani MA, Hajkova P.: Naive pluripotency is associated with global DNA hypomehtylation. Nat Struct Mol Biol. 2013 Feb 17;20(3):311-6.

Hajkova P, Jeffries SJ, Lee C, Miller N, Jackson SP, Surani MA: Genome wide reprogramming in mouse germ line entails the Base Excision Repair pathway. Science. 2010 Jul 2;329(5987):78-82.

Hajkova P. Ancelin K, Waldmann T, Lacoste N, Lange UC, Cesari F, Lee C, Almouzni G, Schneider R and MA Surani: Chromatin dynamics in the process of epigenetic reprogramming in the mouse germ line. Nature. 2008 Apr 17;452(7189):877-81.

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