Cell State Transition Dynamics



Building a Dynamic Landscape of Cell State Transitions

I am interested in understanding how cells rewire their identity as they transition through cell states during development. Studying these transitions is crucial to understand not only how cells enact a developmental program that results in an adult organism, but also how stem cells replace worn or damaged cells to maintain tissue function over time or what goes wrong in disease.

Despite their prevalence and importance, mechanistic understanding of cell fate transitions is hampered by a key challenge: cell states, and corresponding cell behaviour, are emergent properties. A cell state results from the interaction of elements acting at the level of chromatin, gene expression and protein activity, and changes at a single level (e.g. gene expression), do not necessarily allow us to identify when cells change state.

To tackle this problem, I have developed experimental strategies that allow me to directly and quantitatively measure emergent properties (i.e. cell behaviour). With this approach I will:

  1. Map changes to emergent properties to identify when functional cell state transitions occur, e.g. at what point a stem cell becomes a committed progenitor.

  2. Determine the dynamics of transitions, and whether cells gradually change properties over time or if there is an abrupt boundary between cell states.

  3. Identify how signalling pathways, and signalling pathway dynamics, control transition between distinct cell states across molecular scales.

By combining single-cell and embryo-like models, I will also determine to what extent, and if so how, groups of cells collectively coordinate their behaviour (and/or signalling activity) as they undergo state transitions, and to what extend coordination is necessary to ensure robust and reproducible development.

Answering these questions will provide fundamental insight into parameters that typically underlie mathematical models of cell fate choice and allow me to parametrise a dynamic landscape of cell fate decisions.

Please get in touch if you want to hear more.