Functions & Applications of a Novel Stem Cell Signalling Pathway

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The Findlay lab employs cutting-edge technologies to unravel Embryonic Stem (ES) cell signalling networks (Williams et al Cell Rep 2016, Fernandez-Alonso et al EMBO Rep 2017, Fernandez-Alonso et al J Mol Biol 2017, Bustos et al Cell Rep 2018, Fernandez-Alonso et al Nat Commum 2020, Bustos et al Dev Cell 2020), culminating in our discovery of the ERK5 pathway as an exciting new regulator of ES cell pluripotency. In order to uncover functions of ERK5 in ES cells, this project will deploy global proteomic and phosphoproteomic profiling, and transcriptomic technologies such as RNA-SEQ and ChIP-SEQ. Novel ERK5 substrates and transcriptional networks will be identified and characterised using biochemical and ES cell biology approaches. A further aim is to investigate functions of ERK5 in human patient-derived iPS cell maintenance and lineage-specific differentiation to neurons, cardiomyocytes etc. This research will be undertaken in the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), one of the world's leading centres studying the role of cell signalling in health and disease. Students will have access to state-of-the-art tools to dissect signalling networks, and opportunity for interaction with three major Pharmaceutical companies that support the MRC-PPU via the Division of Signal Transduction Therapy. The Findlay lab is also affiliated with the Division of Cell and Developmental Biology, which comprises world experts in stem cell research. The applicant will also work closely with second supervisor Vicky Cowling to dissect mechanisms by which ERK5 regulates transcription and gene expression.