Analysis of progenitor cell differentiation programmes
Applicants (UK, EU and international) capable of self-funding or with scholarship are welcome to apply.
Cell differentiation programmes are central to the production of specialised tissues during development. Moreover, in-depth understanding of cell differentiation is essential for many applications, including stem cell technology and tissue repair. We study the programme that governs muscle formation. This is important not only because muscle is a major cell type and an established paradigm for cell differentiation, but also because of its significance for human health. You will analyse the control of when and where muscle differentiation occurs and how this differentiation programme is orchestrated. You will use the classic, genetically tractable, model organism Drosophila melanogaster, which has shaped much of our understanding of animal development and has an impressive history of informing human biology and medicine. You will analyse the differentiation of both embryo and adult progenitor cells, the latter in remodeling and regeneration during metamorphosis.
Progenitor cell differentiation is controlled by a balance of factors. A key promoting factor for muscle is the conserved Mef2 transcription factor. We found that expression of different muscle genes requires different levels of Mef2 activity (PNAS 105:918-923 (2008)). This highlights the importance of understanding how Mef2 activity is regulated, which is the focus of this project. We also recently identified a novel regulator, Him, that down-regulates Mef2 activity and inhibits muscle differentiation (Current Biology 17:1409-13 (2007)). You will analyse both Him and other Mef2 regulators, including those identified in an ongoing screen, and also assess Mef2 activity during muscle differentiation using in vivo Mef2 sensors. Together, this will indicate how Mef2 can co-ordinate the expression of diverse muscle genes and unravel mechanisms that maintain progenitor cells in an undifferentiated state.
The host lab offers valuable training possibilities through interactions with labs across Europe and the opportunity to use a broad range of techniques from molecular cell biology and genetics.