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Quantitative biology of cell fate and tissue dynamics: Modelling stem cell fate and alterations due to mutations

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  • Full or part time
    Dr E Morrissey
  • Application Deadline
    No more applications being accepted
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The group uses a combination of deep learning, stochastic models and Bayesian modelling to study questions relating to stem cell fate dynamics and how mutations in stem cells alter their normal behaviour, become fixed and accumulate in the tissue eventually leading to cancer. The group is made up of members with quantitative backgrounds (Theoretical Physics, Maths and Engineering) and would particularly welcome somebody with a similar type of background, for instance in Physics, Mathematics, Engineering, Statistics or Computer Science.

Currently we work on two main systems, the intestinal crypt and the haematopoietic system, both of which are fuelled by adult stem cells. The kind of questions we work on relate to understanding how stem cells make fate choices and how these choices lead to homoeostatic balance dynamics [Kozar et al 2013, Vermeulen et al 2013]. Also we study how these homoeostatic balances are disrupted by mutations and how the mutations spread through the tissue [Vermeulen et al 2013, Nicholson et al 2018].

We work in close collaboration with experimental scientists, in the WIMM and elsewhere (Cambridge, Cardiff, Canada), working with both cellular and molecular data. We develop modelling and statistical machine learning approaches to study and understand these systems. Some possible PhD areas to work on are blood cell mutation propagation in collaboration with experimental scientists at the WIMM, the relation between cell division properties and fate or stochastic modelling of single cell data in relation to tissue homeostasis.

The mathematical and statistical techniques that will be used cover a broad range of topics and will include deep learning, stochastic modelling, diffusion models and Bayesian Inference. Training and mentoring will be provided, so prior knowledge of these techniques is not necessary.

As well as the specific training detailed above, students will have access to high-quality training in scientific and generic skills, as well as access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

All MRC WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the MRC WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework.

Funding Notes

Our main deadline for applications for funded places has now passed. Supervisors may still be able to consider applications from students who have alternative means of funding (for example, charitable funding, clinical fellows or applicants with funding from a foreign government or equivalent). Prospective applicants are strongly advised to contact their prospective supervisor in advance of making an application.

Please note that any applications received after the main funding deadline will not be assessed until all applications that were received by the deadline have been processed. This may affect supervisor availability.

References

Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium. Nicholson AM, Olpe C, Hoyle A, Thorsen AS, Rus T, Colombé M, Brunton-Sim R, Kemp R, Marks K, Quirke P, Malhotra S, Ten Hoopen R, Ibrahim A, Lindskog C, Myers MB, Parsons B, Tavaré S, Wilkinson M, Morrissey E, Winton DJ. Cell Stem Cell. 2018 Jun 1;22(6):909-918.e8.

Defining stem cell dynamics in models of intestinal tumor initiation. Vermeulen L, Morrissey E, van der Heijden M, Nicholson AM, Sottoriva A, Buczacki S, Kemp R, Tavaré S, Winton DJ. Science. 2013 Nov 22;342(6161):995-8.

Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. Kozar S, Morrissey E, Nicholson AM, van der Heijden M, Zecchini HI, Kemp R, Tavaré S, Vermeulen L, Winton DJ. Cell Stem Cell. 2013 Nov 7;13(5):626-33.

How good is research at University of Oxford in Clinical Medicine?

FTE Category A staff submitted: 238.51

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