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The epigenetic and transcriptional regulation of adult stem cell pluripotency during regeneration.

  • Full or part time
  • Application Deadline
    Friday, January 24, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

As animals grow and mature all of their cells, tissues and organs must be maintained by the proliferation and differentiation of adult stem cells. As we age the ability of our adult stem cells to perform this homeostatic maintenance declines, particularly in response to physical damage or disease. This leads to physiological ageing. Some animals however have adult stem cells that just keep going, are able to replace any damaged tissue and organs in the body (i.e. are pluripotent) and therefore avoid any effects of physiological ageing. This PhD project will study how these adult stem cells are able to achieve all of this.

We use the highly regenerative planarians model system to study adult stem cells and regeneration in vivo, using state of the art functional genomic approaches (for example RNA-seq, ChiP-seq, ATAC-seq, combined with RNAi knockdown of gene function) to understand the regulatory mechanisms that control regeneration. These animals, fuelled by their adult stem cells, are able to both regenerate the entire body from just small fragments cut from anywhere in the body and to avoid the ageing process entirely (i..e. they are immortal). Currently we do not have a complete understanding of how they do this, but clearly both epigenetic and transcriptional regulatory mechanisms will be key in this process. Our previous work has shown that much of the regulation that controls planarians stem cells uses many of the same epigenetic and transcriptional regulators as our own stem cells.

This PhD project will be aimed specifically at understanding how the pluripotency of planarians adult stem cells, called neoblasts, is regulated. Starting with our existing knowledge of the transcription factors expressed in neoblasts and the epigenetic status of the genome you will perform experiments and bioinformatic analyses that lead to an understanding of the transcriptional network that controls pluripotency, analogous to the Yamanaka factors known to allow reprogramming of differentiated cells to a pluripotent stem cell state in mammals. Both the identity and mechanisms controlled by the equivalent factors in planarian stem cells is currently unknown, but having this knowledge is a key part of understanding how regeneration works and how these animals avoid the ageing process.

Applicants should have a first-class or high upper second undergraduate degree (or equivalent overseas qualification) in a relevant subject (e.g. biology, genetics, biochemistry), your may also have postgraduate experience at Masters level (or similar), and/or some alternative research experience (e.g. laboratory research assistant, extended project work). Interested candidates are encouraged to contact Professor Aziz Aboobaker with (1) a max 1 page statement detailing overall research interests and specific interests in this project, and (2) an up to a 2 page CV.

Funding Notes

Funding is competitive via either University or Departmental Studentships and Scholarships, including the major Doctoral training programmes at Oxford. International students are encouraged to investigate all sources of funding, including Oxford based Scholarships.

References

Aboobaker AA. Planarian stem cells: a simple paradigm for regeneration. Trends
Cell Biol. 2011 doi: 10.1016/j.tcb.2011.01.005.

Mihaylova Y, Abnave P, et al, Conservation of epigenetic regulation by the MLL3/4 tumour
suppressor in planarian pluripotent stem cells. Nat Commun. 2018 Sep 7;9(1):3633.
doi: 10.1038/s41467-018-06092.

Dattani A, Kao D, et al, Epigenetic analyses of planarian stem cells demonstrate conservation of
bivalent histone modifications in animal stem cells. Genome Res. 2018 doi: 10.1101/gr.239848.118.

How good is research at University of Oxford in Biological Sciences?

FTE Category A staff submitted: 223.80

Research output data provided by the Research Excellence Framework (REF)

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