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Dissecting Signaling Pathways – DiSiP

Submission summary

Through evolution, living organisms have developed specific responses to cope with fluctuations of their environment such as osmotic shocks, temperature shifts, oxidative damages, chemical toxicity... To do so, a single cell has to detect environmental changes (specialized sensor proteins), signal those changes to the cell's nucleus (signaling cascade) and transcribe a set of genes that will, hopefully, leads to cell adaptation. Although many signaling pathways architectures are well described in the literature, there are only few quantitative studies concerning their intrinsic timescales and their transfer of information capacity. Time is, however, crucial when responding to harsh stresses such as osmotic shocks. Using the yeast Saccharomyces cerevisiae and its HOG signaling cascade as a model pathway, the DiSiP project will ask how much Information can a given signaling pathway transmit to the nucleus; what are the parameters (physical and biological) that set the signaling timescales and to what extent it is possible to modify those timescales genetically. The DiSiP project will start by improving a prototypal micro fluidic device - designed in a recent work by the project leader [1] - to create a reliable, high frequency, fluctuating environment while allowing for microscopy imaging of fluorescent proteins. Such a tool will then be used to dissect the HOG signaling pathway by studying the frequency response of single mutant cells subjected to an oscillatory environment. This study will result in a fine quantification of the effect of mutation and protein concentrations on the dynamics of the pathway, the ultimate goal being to get insights on how to engineer faster or slower cells with respect to a given stimulus. ...

Project coordination

Pascal HERSEN (Organisme de recherche)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Help of the ANR 200,000 euros
Beginning and duration of the scientific project: - 48 Months

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