Development proceeds via a sequence of decisions that cells have to make about whether to divide, to differentiate, or to migrate. Differentiation is the process by which a cell changes from one type to another, which enables the expansion of the different lineages and growth of the different structures of the adult. Embryonic stem (ES) cells are uniquely naïve in this regard: these cells retain the ability to differentiate to any cell type of the adult body, as well as the germ line. Moreover, experimental techniques allow us to capture and study this state, with the promise of exploiting the potential of ES cells for regenerative medicine.
However, before we can utilise these cells, we need to understand the decisions that they make. In collaboration with leading experimental laboratories at the Universities of Cambridge and Padua, we are combining formal verification, model-checking and model synthesis techniques to uncover the biological programs governing stem cell decision-making.
To date we have made advances in understanding the naïve, pluripotent state: using the Reasoning Engine for Interaction Networks (RE:IN), we sought to characterise the biological program governing the decision to remain self-renewing, or to differentiate. Our work allowed us to derive a mechanistic explanation of a range of experimental observations, and to predict the response of these cells to genetic perturbations accurately. We are now exploring the phenomenon of cellular reprogramming – how lineage restricted cells can be ‘reset’ to the naïve state – as well as the process of differentiation itself.