BBSRC NLD Doctoral Training Partnership: Uncovering the role of NF-κB2 in embryonic stem cell pluripotency and differentiation

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. Indeed, it is unknown whether NF-κB plays a role in defining or refining the route of germ layer differentiation. We have discovered a novel interaction between NF-κB and key components of the cellular metabolism machinery in mouse embryonic stem cells (mESCs), however it is unclear why or how this occurs.

In this project, we will undertake a quantitative analysis of NF-kappaB signalling, coupling bulk biochemistry with single-cell analysis using immunofluorescence, and fluorescently-tagged NF-κB2 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 both 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 Master’s degree in Developmental Biology or related biological sciences discipline.

HOW TO APPLY:

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk 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 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 bbsrcdtp@liverpool.ac.uk. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to david.turner@liverpool.ac.uk

The deadline for all applications is 12noon on Monday 22nd July 2024.

Part-Time Study Options

All NLD DTP PhDs are available as part time or full time, with part time being a minimum of 50% of full time. Please discuss potential part time arrangements with the primary supervisor before applying to the programme.

Project CASE Status

This project is not a CASE project. While individual applicant quality is our overriding criterion for selection, the NLD DTP has a commitment to fund 8 CASE projects per year - as such, CASE projects may be favoured in shortlisting applicants when candidates are otherwise deemed to be equal or a consensus on student quality cannot be reached.