PhD in Biosciences Understanding Cell Differentiation Programs Using A Model Progenitor Cell System

A new PhD position in cell biology is available at Cardiff University. Candidates are welcome before July 19, 2019.

Cell differentiation programs drive the production of specialised tissues from progenitor cells during animal development.

Understanding these programs is critical for many aspects of pure and applied biology, including directing stem cells to make specific cell-types for both analysing disease mechanisms and exploring novel therapies. Key transcription factors regulate organised patterns of gene expression in differentiation programs.

We study the conserved transcription factor Mef2 in muscle differentiation in the classic model organism Drosophila.This is for three main reasons: (i) Mef2 is significant both as a key player in muscle differentiation from progenitor cells and as a model for how protein interactions modulate output from pivotal transcription factors; (ii) muscle is both important for human health and an established paradigm for cell differentiation; and (iii) Drosophila research has an impressive history of informing human biology.

This project builds on our previous work (1-5), which shows that the activity of the Mef2 protein is regulated in time and space (e.g. to stop it activating differentiation genes in progenitor cells, and then to produce sequential gene activation in the differentiation program). This regulation results from interactions with other proteins. However, little is known about these interactions and how Mef2 activity is modulated in vivo, and this will be the focus of your project. You will have the opportunity to use diverse techniques from molecular cell biology and genetics. For example, CRISPR/Cas9 methodology, and analysing protein interactions with Mef2 using the classic yeast two-hybrid approach and FRET/FLIM, a new optical approach to analysing protein interactions in vivo.


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