Cell fate circuits: Sensor and actuators of reprogramming

DESIGNING SOFTWARE TO MATCH HARDWARE

Scaling circuit output to match cellular capacity

Tradeoffs between transcription and replication limit cellular reprogramming, with excessive transcription limiting necessary cellular division. To effectively balance these tradeoffs, our lab constructs control systems to tailor expression of reprogramming factors to cellular capacity.

MEASURING TRANSITION SPEED

Characterizing the dynamics of proliferation-mediated transitions between cell states

By examining the process of cellular decision-making in the synthetic context of reprogramming, we examine the contribution of developmentally-entangled systems-level phenomena (e.g. transcriptional activity, proliferation) to cell state switching. State transitions from one cell fate to another represent transitions in large transcriptional networks that may be approximated by transitions in small transcriptional networks (e.g. a bistable switch), which can be more easily measured, modified, and modeled.  Using a synthetic circuit as a probe, my lab will characterize how direct conversion and hyperproliferation affect the dynamics of transitions within a bistable circuit.