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. 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-𝜅B signalling is central to many cell-fate decisions, although its role in early mammalian development is highly controversial. NF-𝜅B is also highly dynamic, oscillating between the nucleus and cytoplasm the frequency of which can modulate gene expression. However, it is unknown whether NF-𝜅B 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-𝜅B 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-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 research students (PGRs) undertake formal, personalised training at Liverpool, co-ordinated by the Liverpool Doctoral College. This creates a learning environment that allows 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 other related biological sciences discipline.
Informal enquiries may be made to firstname.lastname@example.org
HOW TO APPLY
Applications should be made by emailing email@example.com with a CV and a covering letter, 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. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.
In addition to the CV and covering letter, please email a completed copy of the Application Details Form (Word document) to firstname.lastname@example.org, noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
2) An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells; Biology Open (2014).
3) Physiological levels of TNF𝛼 stimulation induce stochastic dynamics of NF-𝜅B responses in single living cells; Journal of Cell Science (2010).
4) A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-κB-dependent liver regeneration and cancer Oncogene (2016).
5) Oscillations in NF-𝜅B Signaling Control the Dynamics of Gene Expression; Science (2004).
6) Pulsatile Stimulation Determines Timing and Specificity of NF-𝜅B–Dependent Transcription; Science (2009).
7) Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids; Nature (2018).
8) Anteroposterior polarity and elongation in the absence of extra-embryonic tissues, and spatially localised signalling in gastruloids: mammalian embryonic organoids; Development (2017).
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