Laboratoire Matière et Systèmes Complexes

Deux séminaires consécutifs d’une demie-heure : Artémis LLAMOSI et Jean-Baptiste LUGAGNE.

Artémis LLAMOSI , Matière et Systèmes Complexes, Université Paris Diderot.

The cost of cellular adaptation to stress : a tradeoff between short-term and long-term adaptation to osmotic stress in S. cerevisiae.

Upon stress, cells have evolved complex adaptation strategies to environmental variations which include sensing, information processing and modification of metabolic and transcriptional activity. The reaction of yeast cells to hyperosmotic stress spans several timescales and includes massive gene-expression changes, bio-compatible osmolyte production, and direct action on the cell cycle. Despite a detailed knowledge of molecular events, the impact of stress-response on cellular resources is poorly known. In particular, fitness costs which alter proliferation in the short term while conferring advantage on the long term are important drivers of stress-response evolution.

In this study, we use microfluidics to vary dynamically both the source of cost (osmotic stress) and the available metabolic resources (glucose) while monitoring cellular proliferation. We show that, under hyper osmotic stress, metabolic resources are rerouted towards the production of glycerol through activation of an essential enzyme in glycerol production. This reveals the nature of the burden imposed by osmotic stress and, more generally, allows us to better understand the evolutionary tradeoffs between stress response and proliferation.

Jean-Baptiste LUGAGNE, Matière et Systèmes Complexes, Université Paris Diderot

Long term real-time control of a genetic inverted pendulum in escherichia coli

Multi-stability is a key element of gene regulatory networks and plays a central role in genetic signal processing, cellular decision-making, differentiation and morphogenesis. Unfortunately, because of the intricate behaviour of such networks, understanding and interfacing them with other cellular processes proves a challenge to systems and synthetic biology. To circumvent these problems, we developped an external control platform combining microfluidics, epifluorescence time-lapse microscopy, image analysis and control theory to allow for real-time single-cell control of gene expression in bacteria. We use the platform to demonstrate the potential of external control by inverting the stability of a multi-stable system, the genetic toggle switch. The genetic toggle switch is a bistable network consisting of two genes mutually repressing their expression. This topology features an unstable saddle equilibrium point, and we show that our platform can not only be used to switch the state of the system, but also to maintain it in an unset state around the unstable point through dynamic control, similarly to the benchmark control problem of the inverted pendulum. We then go on to show that this inversion of the stability of the system can be achieved without closed-loop control through dynamic stimulations that could be used in natural systems or synthetic systems for delaying decision-making.