Cell fate decision-making in complex signalling environments

Our goal is to determine how cells integrate multiple signalling inputs to decide their fates. Understanding how cells can respond to this complexity of inputs has, until recently, been intractable because the ability to simultaneously measure the inputs and outputs for individual cells in their population context has been out of reach.

We have developed methods to image transcription in living cells, and this can now be combined with measurements of signalling and cell behaviour over the time and length scales of a developmental fate choice. This means we can continually monitor multiple inputs and outputs of the decision-making process in the context of the entire heterogeneous cell population. Combined with multi-scale mathematical modelling, our approaches will determine:

1. How cells integrate multiple external signals to choose between proliferation and differentiation.

2. How cells reinforce the choice to differentiate and become resistant to signals promoting proliferation.

3. How initial cell state, signalling and cell state transitions influence the final fate of the cell.

Overall our work will define the fundamental characteristics of how the history of exposure to signalling is integrated to generate a fate decision.