Posts Tagged ‘biology’

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:

1) How do individual enhancers read information from a genetic network of interconnected transcription factors?

2) How is this information transferred from the activated enhancer to its target promoter, often over large genomic distances?

3) How is information eventually transformed into a transcriptional output at the level of the promoter?

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.

Introducing a new biophysics laboratory in Princeton’s physics department

Starting February 2009 I will join the Physics Department at Princeton as a new faculty member. I will also be associate faculty of the Lewis-Sigler Institute for Integrative Genomics and of the Molecular Biology Department.

I will teach classes both for the Physics Department and for the Lewis-Sigler Institute. My research is highly interdisciplinary, and my hope is to work closely with students from many science departments across campus, mainly physics, biology, computer science, engineering and applied mathematics.

The research focus of the lab is at the interface of biological physics and systems biology. In particular, understanding embryonic development from the perspective of a physicist that views this highly complex process as a self-assembly problem: How do the different parts and ingredients that originate as a single cell work together to develop into a fully-functioning living animal?

This process of biological self-assembly I am also trying to tackle by looking at the emergence of collective behavior in starved amoebae populations. Here, originally autonomous amoebae display a survival strategy in the face of starvation that leads to a multi-cellular organism that produces spores. This system is very accessible experimentally to understand cell signaling, early stages of cell differentiation and pattern formation and the emergence of collective behavior that leads to multicellularity.

Our research will be mainly experimental, but with a strong theoretical influence, both within the lab and in close collaborations with theorists on campus and elsewhere. On the experimental side the goal is to watch life unfolds, i.e. in vivo measurements and manipulations. We build state-of-the-art microscopes and microfluidics devices, and we make heavy use of tools from molecular biology and genetics. On the theoretical side we design analytical and numerical models both to test and guide our experiments, and we take advantage of tools from computer science to analyze images and large data sets.

A new laboratory is under construction at the moment in 125 Jadwin Hall, the first floor of the physics building next to the stadium. My office will be located on the same floor.