Michael Elowitz uses synthetic biology, time-lapse movies, and mathematical modeling to study gene circuit architecture and dynamics down to the level of individual cells. His laboratory works on problems in differentiation, cell-cell signaling, and stress response. He focuses particularly on the role that stochastic fluctuations (noise) play in living cells.
Using Movies To Analyze Pulsatile Dynamics in Individual Cells
Genetic circuits regulate cellular behaviors. Although many genetic circuits have generally been regarded as homeostatic regulatory systems, movies of individual cells are beginning to reveal surprisingly dynamic modes of regulation based on behaviors such as pulses and oscillations that persist even when cells are maintained in constant conditions. These dynamics appear in a variety of pathways, molecular species, and organisms, and because they are not synchronized between cells, their dynamics can be observed only using movies of individual cells. Interestingly, these dynamics can enable critical signal-processing capabilities that we are only beginning to understand.
In this project, we will analyze pulsatile regulatory systems in bacteria or yeast by engineering strains that allow monitoring and control of these dynamics as well as recording the behavior of individual cells in quantitative time-lapse movies. We will analyze resulting data in the context of mathematical models. The goal is to discover and explain new dynamic signal-processing capabilities in different regulatory pathways.
Synthetic Developmental Signaling and Patterning Circuits
Signaling pathways enable communication between neighboring cells and can be used to coordinate cell fate decisions and create sharp boundaries or "fine-grain" patterns during development. Recently, it has become possible to analyze signaling dynamically at the single-cell level using cell lines that allow us to control pathway component levels and read out signaling pathway activities in time-lapse movies.
Using this approach, we recently showed that interactions between Notch and its Delta ligand force individual cells to either send or receive signals, but do not permit them to do both at the same time. This observation suggests that Notch signaling between two cells can proceed in only one direction at a time.
This project will try to understand the functional roles of different signaling pathways, rewire these pathways to test specific hypotheses, and use them to construct artificial patterning behaviors in cells. The project may also involve a mathematical modeling component in which the consequences of the observed signaling behaviors for developmental networks are analyzed.