Overview

Cells in metazoans are remarkable in their ability to cooperate to form tissues with correct size and function. They do so with no precise template and almost no external oversight. Our lab studies the behaviors and properties of cellular systems that underlie this ability to self-organize, allowing tissues to persist and regenerate over decades of adult life.

Integral to our research is the use of theoretical tools to frame questions on cell behavior, and to guide the conception, design and analysis of our experiments. Much of the theory we use is inspired by statistical physics and mathematical population dynamics, but we also let the data draw us to other theoretical disciplines as needed.

On the experimental front, we are interested in particular in using data from ensembles of single cells to identify general principles of fate choice, and specific genes implicated in fate choice and their associated regulation. Single cell methods form a relatively new field and we spend some time developing cutting edge technologies to enable us to look deep and wide.

From our work, and that of others, we now appreciate that many tissues are maintained by cells that make choices stochastically – yet the cell population in these tissues remains strictly controlled. It is far from clear what mechanisms enable choices to be implemented in this way, and whether similar mechanisms are used in different tissues and physiological conditions. Presumably feedback exists between the state of a tissue and the probabilities for individual cells to commit to different fates. Similar choices may also apply for other cell decisions, particularly in embryos or even in tumors. The language of stochastic processes is ideally suited to describe the variability in single cell decisions, and how decisions change in disease. This is an area of investigation that encompasses fundamental questions in biology and addresses practical questions in stem cell science.