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Uncovering the role of NF-κB in embryonic stem cell pluripotency and differentiation


   Faculty of Health and Life Science

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  Dr D Turner, Prof N Perkins, Prof Mike White  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This exciting project offers an opportunity for a motivated student to contribute to new understanding of the cellular decision mechanisms that control the fate of cells in the early embryo. NF-𝜅B signalling is central to many cell-fate decisions, although its role in early mammalian development is highly controversial. However, our work has recently uncovered a novel role for NF-κB in regulating the decision of mouse embryonic stem cells (mESCs) to remain pluripotent or to differentiate.

In this project, we will undertake a quantitative analysis of the NF-κB signalling in mESCs during pluripotency and differentiation, coupling bulk biochemistry with single-cell analysis using immunofluorescence, and fluorescently-tagged NF-κB proteins. We will target up-stream components of the NF-κB signalling cascade with small molecule inhibitors to disrupt the signalling and assess how it alters pluripotency, and differentiation. New fluorescent cell lines will be developed to allow us to visualise NF-κB dynamics and lineage-specific reporter-gene expression in single-cells over time. This will allow us to extract general principles underlying fate choices during early embryo development, and how the interplay between NF-κB, cell state, and chemical signalling underpins these decisions. 

The supervisory team will provide training and support in all relevant techniques. The student will be based at University of Liverpool, which has developmental biology and cell imaging expertise, and will benefit from the close collaboration with Prof. Mike White (University of Manchester), an expert in single-cell NF-κB dynamics. The student will spend time in Newcastle University with Prof. Neil Perkins, where they will be trained in biochemical techniques to probe the role of post-translational regulation of NF-𝜅B proteins in developmental cell-fate decisions.  

All postgraduate students (PGRs) undertake formal, personalised training at Liverpool, co-ordinated by the Liverpool Doctoral College. This creates a learning environment allowing PGRs to enhance their skills for a successful research career. Participation in public and patient engagement events, for which the host department have won awards, is strongly encouraged. This project is suited to a candidate with a Bachelors (2:1 or above) or Masters degree in Developmental Biology or related biological sciences discipline.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·        a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]

The deadline for all applications is 12noon on Monday 9th January 2023. 


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We 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 only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

Brachyury cooperates with Wnt/β-catenin signalling to elicit primitive-streak-like behaviour in differentiating mouse embryonic stem cells; BMC Biology (2014)
Physiological levels of TNF𝛼 stimulation induce stochastic dynamics of NF-𝜅B responses in single living cells; Journal of Cell Science (2010)
A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-κB-dependent liver regeneration and cancer Oncogene (2016)

Oscillations in NF-𝜅B Signaling Control the Dynamics of Gene Expression; Science (2004); Directly relevant: first time NF-𝜅B oscillations were seen in single-cells
Pulsatile Stimulation Determines Timing and Specificity of NF-𝜅B–Dependent Transcription; Science (2009)
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