Regulation of growth and differentiation of embryo derived stem cells.

Our Lab’s research interests centre on the regulation of growth and differentiation of pluripotent embryonic stem (ES) cells. The ability to expand these remarkable cells indefinitely in culture and then differentiate them into somatic and germ cell lineages provides unique opportunities to study mammalian biology and promises to revolutionise drug discovery and regenerative medicine. Recent “paradigm shifting” work from Professor Shinya Yamanaka’s laboratory on inducing pluripotency in somatic cells now makes it now feasible to consider generating genotype-specific pluripotent cell lines without relying on embryonic source tissue. Nevertheless, despite these spectacular advances, efficient expansion of large numbers of karyotypically and phenotypically normal embryonic stem cells is not trivial: there is a pressing need to better understand how to stably propagate these cells in culture and predictably and quantitatively control their differentiation.

The main area of investigation in the lab is how intracellular signals regulate ES cell growth and differentiation. This work focuses principally on the activity of the MAPK and PI3K pathways and involves: i) examining the role of established ES cell regulators (i.e. adaptor protein Grb2), ii) characterising the function of a novel ES cell specific regulator in mouse ES cells (a Grb2-binding protein 1 variant) and iii) investigating signaling cross-talk between pathways. We also aim to further define the core regulatory pathways regulating pluripotency in mammals by comparing cells from different species. To this end, the Roslin Institute has initiated a programme to derive new embryonic cell lines from rats and farm animals.

Lineage specific fate determination in the early embryo or ES cells requires the suppression of both pluripotency and alternative differentiated fates. Recent studies suggest that this can be mediated at the post-translational level by micro RNAs. Together with Dr Michael Clinton at the Roslin Institute we have begun examining the role miRNAs play in regulating early embryonic differentiation. 

Obtained a first class degree in Biology at the University of York in 1984, and completed my PhD at the University of Nottingham in 1988. To develop my research interests in molecular genetics of mammary gland differentiation, I took post-doctoral positions at NIH (Bethesda MD/Beltsville MD) and then at the Roslin Institute. During the latter post-doc, I became interested in how cytokine signalling regulated differentiation, and decided to join Austin Smiths laboratory (CGR/UoE) to study the role of LIF signalling in embryonic stem cells (ESCs). In 2002 I established my laboratory at the Roslin Institute investigating the control of growth and differentiation of embryo derived stem cells. Since 2008 the lab has exploited rat ESCs as a tool for rat transgenesis and elucidating new mechanisms that control self-renewal and pluripotency. Currently we are continuing these basic studies, and extending our work to developing novel stem cell systems for directed differentiation and the functional analysis of genetic variation in livestock species.   

Understanding the coontrol of growth and differentiation in pluripotent stem cells, and exploring their potential for functional analysis of genetic variation in livestock species.