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  Erk5-Dependent Mechanisms Which Determine Embryonic Stem Cell Identity


   Protein Phosphorylation and Ubiquitylation Unit

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  Dr Greg Findlay  Applications accepted all year round  Competition Funded PhD Project (European/UK Students Only)

About the Project

Pluripotent Embryonic Stem Cells (ESCs) have the capacity to differentiate into all specialized cell types, including brain, heart, lung, liver and pancreas. ESC identity is tightly controlled by protein kinase signaling, which our lab seeks to exploit towards the application of ESCs in tissue regeneration. In a small molecule kinase inhibitor screen, we uncovered a critical function for the Erk5 kinase in controlling ESC pluripotency. Using inhibitor engineering and CRISPR/Cas9 genome editing, we show that Erk5 modulates transition between “naïve” and “primed” pluripotent ESC states. Excitingly, we also find that Erk5 restrains cardiac specific gene expression and differentiation of ESCs to functional cardiomyocytes.
This project aims to apply cutting-edge technologies to unravel the molecular mechanisms by which Erk5 controls ESC identity. The successful applicant will use phosphoproteomics to identify Erk5 substrates, and total cell proteomics and RNA-SEQ transcriptomics to explore the wider role of Erk5 in regulating protein-coding and non-coding gene expression. This knowledge will then be exploited to promote cellular reprogramming and differentiation of cardiac tissue from pluripotent cells.

Funding Notes

We offer a 4 year studentship in which you would join a particular lab in the Unit. However, we strongly encourage prospective students to become part of the 4-year PhD programme in which you carry out rotation projects in two labs within the Unit (http://www.ppu.mrc.ac.uk/studentships/phd_projects.php). This studentship is jointly funded by the Medical Research Council and the University of Dundee and carries a tax-free stipend of £20,000 per annum