Professor Chris Thompson (MA, PhD) - research
Cell fate choice and pattern formation in Dictyostelium
Developmental cell fate choice and proportioning is characterised by its robustness and reproducibility. Consequently, heterogeneity (also termed noise and stochasticity) in cell behaviours, cell signalling and responses are often thought to be a hindrance. However, recent observations of ‘salt-and-pepper’ differentiation, which is seen in examples raging from competence in B. subtilis, lineage specification in the mouse blastocyst, to stalk and spore differentiation in Dictyostelium have challenged this view. In fact, in these cases such heterogeneity has been proposed to be required for normal cell fate choice and symmetry breaking. Our research addresses the extent to which such heterogeneity is necessary, how something that is inherently variable can be harnessed to result in a reproducible outcome, and what is the source of this heterogeneity.
Our most recent studies (Chattwood et al, eLife 2014) revealed that the interplay between dynamic heterogeneity in Ras-GTPase activity and heterogeneity in nutritional status is required for normal lineage priming and salt and pepper differentiation. This is because such heterogeneity sets the intrinsic response threshold to lineage specific differentiation signals. Indeed new RNA seq data reveals that both conditions bias cells towards the same cell fate (ie the outcome of the bias at the slug stage is identical). Despite this, we find that a surprising inverse relationship between genes under Ras and nutritional control during growth when lineage priming takes place (ie opposite gene expression profiles lead to the same fate outcome). We have used modelling and experimentation to explain this observation, which reveals the existence of a novel system required to buffer against extrinsic variation. We are currently studying how this system facilitates the robust running of an ultradian cell fate oscillator.
Genes involved in conflict and cooperation
During Dictyostelium development, 20% of the cells die to make a cellular stalk. This represents a problem of altruism and cheater control: since stalk cells sacrifice themselves to aid spore dispersal, what prevents the emergence of cheaters that gain the benefit without paying their fair share of the cost? We study lab generated cheater and loser mutants and genes to define the pathways that control cell fate choice and social behaviour.
P2X receptor function and regulation
P2X receptors are ATP gated ion channels that regulate responses to extracellular ATP. However, we recently discovered an intracellular function for a P2X receptor in Dictyostelium, thus raising new questions about their role and regulation. In addition, several other Dictyostelium P2X receptors exist and little is known about the regulation of P2X receptors or their downstream effectors in any organism. We are using the genetic, proteomic and post-genomic tools available in Dictyostelium to address these questions.