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. These numerous, discrete cell-fate decisions are often binary in nature, however, the processes by which individual cells actively adopt one fate at the expense of another is still an unresolved key question in biology.

NF-?B signalling is central to many cell-fate decisions, although its role in early mammalian development is highly controversial. NF-?B is also highly dynamic, oscillating between the nucleus and cytoplasm the frequency of which can modulate gene expression. However, it is unknown whether NF-?B expression or its dynamics play a role in defining or refining the route of germ layer differentiation.

We take an embryonic stem cell (ESC) approach to dissect the role of NF-?B signalling during in early development, focussing on the cell-fate decisions that lead from pluripotency (the ability to generate all tissue and cell types of the embryo proper) to differentiation, using a combination of high-end, state of the art single-cell time-lapse fluorescence microscopy, coupled with gene expression analyses and biochemical techniques. New fluorescent cell lines will be developed to allow us to visualise both NF-?B 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-?B, 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-?B 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-?B proteins in developmental cell-fate decisions. 

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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.

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