In the early mammalian embryo a group of cells form that have the special property of pluripotency. Pluripotency is the developmental potential of a cell to generate the founder lineages of the embryo: endoderm, mesoderm and ectoderm. The fate of a pluripotent cell is not pre-determined but is decided by regulatory signals. Pluripotent cells taken from embryos can be converted into immortal stem cells in the laboratory by manipulating these signals. In addition, by molecular reprogramming can be used to induce pluripotent stem cells from somatic cells (Takahashi et al., 2007).
Crucially, the competence of pluripotent cells to respond to instructive signals for differentiation changes over time. The first pluripotent cells to emerge in the embryo are termed naïve because they have high potential but are unable to differentiate directly into embryonic lineages. They must first transition to a second stage of pluripotency, termed formative (Smith, 2017), in which competence is gained for lineage differentiation. The molecular machinery underlying competence is poorly understood but is central to the temporospatial pattern of embryonic lineage formation. Knowledge of the competence process will facilitate our ability to direct differentiation in vitro for biomedical applications.
In human the formative transition takes place over several days, both in culture and in the embryo (Rostovskaya et al., 2019; Tyser et al., 2021). The goal of this PhD project is to build on and complement current investigations characterising the stepwise gain of competence and the underpinning molecular switches. A particular focus will be to derive formative pluripotent stem cells corresponding to different stages of transition and potentially with distinct developmental competencies. The research will be centred around genetic and signalling manipulations of stem cell cultures. Transgenic reporters will be engineered to monitor signalling activity and transcription factor expression in living cells by flow cytometry and advanced microscopy. Accompanying molecular and biochemical analyses will extend to ‘omics studies and gene regulatory network analysis. Depending on the interests of the student there will be collaborative opportunities for mathematical modelling of network dynamics.
The research will be carried out in the interdisciplinary Living Systems Institute where biologists, mathematicians and physicists collaborate to understand the properties and functions of cells, the basic units of life. You will join a community of more than 50 PhD students on the LSI PhD Programme.
Candidates will have first-hand experience in laboratory research. You will be enthused by fundamental science, motivated to discover new knowledge, and eager to develop your own ideas.
This award provides annual funding to cover Home tuition fees and a tax-free stipend. For students who pay Home tuition fees the award will cover the tuition fees in full, plus at least £17,668 per year tax-free stipend. Students who pay international tuition fees are eligible to apply, but should note that the award will only provide payment for part of the international tuition fee and no stipend.
International applicants need to be aware that you will have to cover the cost of your student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.
The conditions for eligibility of home fees status are complex and you will need to seek advice if you have moved to or from the UK (or Republic of Ireland) within the past 3 years or have applied for settled status under the EU Settlement Scheme.
Entry requirements
Applicants for this studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology.
If English is not your first language you will need to meet the required level (Profile B) as per our guidance at https://www.exeter.ac.uk/pg-research/apply/english/
How to apply
In the application process you will be asked to upload several documents .
• CV
• Letter of application (outlining your academic interests, prior research experience and reasons for wishing to undertake the project).
• Transcript(s) giving full details of subjects studied and grades/marks obtained (this should be an interim transcript if you are still studying)
• Two references from referees familiar with your academic work. If your referees prefer, they can email the reference direct to [Email Address Removed] quoting the studentship reference number.
• If you are not a national of a majority English-speaking country you will need to submit evidence of your proficiency in English.
The closing date for applications is midnight on Friday 10th February 2023
If you have any general enquiries about the application process please email [Email Address Removed] or phone 0300 555 60 60 (UK callers) +44 (0) 1392 723044 (EU/International callers) .
Project-specific queries should be directed to the main supervisor Professor Austin Smith,
For further information and to submit an application please visit - https://www.exeter.ac.uk/study/funding/award/?id=4535
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