The Roslin Institute
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.