HERSEN | Dynamic Control of Signaling and Gene Expression

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Pascal Hersen Team Leader

We are an interdisciplinary team working at the frontier of physics and biology. We use microfabrication, microfluidics, fluorescence microscopy, synthetic biology and cell biology to dynamically play with cells, their signaling pathways and their gene regulatory networks. Our long term goal is to control cellular processes in space and time, with a specific focus on : Cybergenetics (or the ability to interact with cellular process and control them in real time) and Synthetic embryology (or how to study the emergence of spatial organization of tissues in vitro). We are constantly looking for highly motivated and highly skilled researcher and students with a taste for instrumentation, coding, synthetic biology and a strong interest for physics (of life). Do not hesitate to contact us if you feel that you can contribute to our team.

Research

Cybergenetics – Real Time Control of gene expression.

Regulation of gene expression is a central problem in biology. Cellular homeostasis requires a fine tuning of essential biological functions (e.g. response to stress, metabolism…) through the activation of specific regulatory pathways. In order to decipher the logic of genetic networks classical approaches have long used specific toolsets (e.g. knock out genes, gene over-expression) to alter protein levels and observe the changes in cellular physiology. Although this methodology has proven very successful, it is limited to static and unprecise changes. This means that whereas the functional role of most proteins is known, their quantitative influence on the properties of their regulatory network is not easily accessible. Therefore, having a mean to externally control, in real time, the expression level of a gene of interest would be a major step towards a better, quantitative understanding of how a cell functions. This motivated us to develop a real time, computer based, control of gene expression in live cells which can be seen as a cell-computer interface to control gene expression. We are pioneers in this field, known as Cybergenetics, and are actively working on its development and applications to biology.

Synthetic embryology – Spatial Control of gene expression.

One striking property of embryonic tissues is their ability to self-organize in order to form well-defined patterns that prefigure the body plan. Combining the biophysics experimental toolbox (microfluidics, micro-fabrication,micro-patterning, advanced microscopy, modeling…) to Embryonic Stem Cells culture, we are designing in vitro model systems that allow us to study the minimal ingredients required for spatial organization and the relationship between an external cue (such as a morphogen gradient) and tissue organization.