Using physics to study life
My laboratory is interested in problems at the interface of physics and biology. The main thrust of our research is the design of new experimental approaches and performing high-precision physics-style measurements in living animals, such that our data allows for direct validation of mathematical models. This program is aimed at the generation of theories describing biological phenomena which are derived from general principles in the physics tradition. Currently, our primary interests lie in the self-organization and collective behaviors of eukaryotic cell aggregates, from microbes to embryonic tissue, and in how the control of gene expression in early fly embryos leads to the formation of an animal body plan. We are making experimental and theoretical progress on the biological questions in each of these areas but the long-term goal is to find theories inspired by experimental data that go beyond the specifics of the biological systems hoping to find in the living world new physics, which has been hidden and cannot quickly be revealed in the inanimate world. The approach outlined here extends the traditional physics approach, which my colleagues used to study the stars or inert matter on Earth, to the complex processes underlying the living world.
The laboratory is currently composed of two research facilities working on similar topics and questions. One at Princeton University, since 2009, and since recently (2018) a second laboratory at the Institut Pasteur in Paris (France). The laboratory in Princeton works with Drosophila melanogaster models for which we have developed many highly quantitative imaging technologies to perform precision measurements in living embryos. At the unit at Institut Pasteur, we implement derivatives of these technologies in mammalian model systems such as mouse embryonic stem cells and stem cell-derived embryoid cell aggregates (i.e. gastruloids). Once these perform at similar levels of precision to what we achieve with the fly system, we will assess physical concepts such as developmental precision and reproducibility, system size scaling, or self-organization phenomena across both model systems.
Activities at Princeton will continue with the Drosophila model along the following directions: studying the flow of information from molecules to macroscopic patterns, where cells determine their identity by interpreting this information from a genetic network of interconnected transcription factors. With the gene regulatory sequence, the enhancer, still at the core of our investigation, we identified three central questions that we will continue to address during the next cycle:
To answer these questions, several technologies are being developed, namely live single-molecule imaging and optogenetic perturbation of single cells and individual gene loci in living embryos.