Protein interactions in the regulation of a model cell differentiation program

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. Key transcription factors regulate organised patterns of gene expression in differentiation programs.

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

The project builds on our previous work (1-4), which shows that Mef2 activity is regulated in time and space (e.g. to stop it activating target genes in progenitor cells, and to produce sequential gene activation in the differentiation program). This regulation must result from interactions with other proteins. However, little is known about these interactions and how Mef2 activity is modulated in vivo. You will analyse these protein interactions, concentrating on several proteins already implicated in our lab, together with new proteins from on going screening. You will have the opportunity to use diverse techniques from molecular cell biology and genetics (e.g. the new FLIM approach to analysing protein interactions in vivo using pulsed laser confocal microscopy) and to access valuable training through interactions with labs across Europe.