3.5 Year MRC PhD Programme: Exploiting ERK5 signalling in regenerative medicine: a novel route to cardiac regeneration.

Pluripotent Embryonic Stem Cells (ESCs) have the capacity to differentiate into all specialized cell types, including brain, heart, lung, liver and pancreas. ESC decision-making is tightly controlled by cellular signaling networks, which our lab seeks to unravel and exploit to elaborate novel ESC-based cell replacement strategies (Fernandez-Alonso et al, 2017). In a recent small molecule kinase inhibitor screen, we uncovered a critical function for the ERK5 signalling pathway in controlling ESC pluripotency. Using inhibitor engineering and CRISPR/Cas9 genome editing, we find that ERK5 modulates transition between “naïve” and “primed” pluripotent ESC states. Excitingly, we also identify a new role for Erk5 in restraining cardiac specific gene expression and differentiation of ESCs to cardiomyocytes (Williams et al, 2016).

This project will apply cutting-edge technologies to unravel 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. A further aim is to identify molecular mechanisms that activate ERK5 signalling in ESCs, and exploit this information to reprogram somatic cells to naïve pluripotency. You will work closely with the Human Pluripotent Stem Cell Facility in the School of Life Sciences, using specific ERK5 inhibitors and CRISPR/Cas9 genome editing to investigate the role of ERK5 in human induced Pluripotent Stem Cell (hiPSC) maintenance, cardiac differentiation and cardiomyocyte function and physiology. Ulitmately, this knowledge will provide new routes towards cellular reprogramming and differentiation of cardiac tissue from pluripotent cells.

The University of Dundee is delighted to be recruiting for five PhD studentships, funded for 3.5 years, to start in September 2017. These projects bring together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK.

Eligibility: Applications for these MRC studentships are invited from excellent UK* students expected to hold (or be about to achieve) at least a 2:1 Honours degree in a relevant subject.
*Some EU students may be eligible for a full award if you meet Research Council residency criteria and other exceptions may apply.