Using Synthetic Biology to Investigate Embryonic Stem Cell Signaling

Using Synthetic Biology to Investigate Embryonic Stem Cell Signaling

Although it is clear that sophisticated signaling networks control most aspects of development and disease, pin-pointing the key regulatory attributes of complex biological systems is increasingly challenging. My research aims to address this problem using synthetic biology in embryonic stem cells, an approach which has uncovered defining mechanisms of cell fate control. Firstly, by re-wiring the key FGF4-Ras-Erk pathway, I show that the Sos1/Grb2 RasGEF complex consists of finely-tuned interaction modules, which cooperatively determine the timing and fidelity of stem cell lineage commitment (Findlay et al., Cell 2013). I also apply protein engineering to generate highly selective protein interactions within the FGF4 signaling network, thereby identifying a single connection that elicits embryonic stem cell differentiation (Yasui*, Findlay* et al., Mol Cell 2014). These studies illustrate how synthetic probes can be used to characterize the regulatory properties of a complex biological system. Finally, I will describe the novel tools and state-of-the-art technologies I use in my own laboratory to continue elucidating the signaling landscape of pluripotent stem cells.

Greg M. Findlay – a brief review of my scientific career Greg was born and raised only a few miles from the University of Dundee, where he started his scientific career as an undergraduate, receiving a BSc (Hons) in Biochemistry in 2001. He performed his PhD research in London at the Institute of Cancer Research, working with Richard Lamb to investigate novel mechanisms of mTOR pathway regulation. In 2007, Greg moved to Toronto, Canada to work with Tony Pawson at Mount Sinai Hospital, where he used synthetic approaches to understand the role of modular interaction domains in regulating embryonic stem cell fate. In January 2014, Greg moved back to the College of Life Sciences at the University of Dundee, where he set up his research group in the MRC Protein Phosphorylation and Ubiquitylation Unit.

The main interest of the Findlay lab is in understanding signaling networks that control embryonic stem cell pluripotency and differentiation.

Dr Greg Findlay from the University of Dundee will be hosted by Dr Rugg-Gunn. If you wish to meet with Dr Findlay, please contact Dr Rugg-Gunn directly.