Understanding cell differentiation programs using a model progenitor cell system

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 significant for human health and an established paradigm for cell differentiation; and (iii) Drosophila research has an impressive history of informing human biology.

The project builds on our previous work (1-4), 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, you will use CRISPR in a structure/function analysis of Mef2. You will also analyse protein interactions with Mef2, initially concentrating on several proteins already implicated in our lab. This will use a range of techniques, for example the classic yeast two-hybrid approach and FLIM, a new optical approach. You will have the opportunity to access valuable training through interactions with labs across Europe.

Start Date: 1st October 2017 (or as soon as possible thereafter)
Duration: 3 years
Please contact supervisor Dr Michael Taylor ([Email Address Removed]) for further details of this project.