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Mutations that modify cell proliferation in repeated stress

Published on : March 12, 2018

The research team of Gaël Yvert at Laboratory of Biology and Modeling of the Cell (LBMC) has discovered mutations that increase cell proliferation in conditions of repeated stress.

 Healthy cells were mixed with cells harbouring a specific gene defect, and this population was cultured in normal condition (blue), continuously-stressful condition (yellow), and in repeated stress (dashed line). Mutant cells become rapidly predominant i
Whether cells divide or not and generate new cells depends on their environment, which, usually, changes dynamically. Some environments are 'stressful' and cells need to adapt their physiology to face such conditions. This adaptive process is well-known when stress occurs once or twice, but not in situations where cells are challenged repeatedly.

What happens then is unkown. In particular, the molecules that drive the dynamics of adaptation in an ever-changing environment are unknown.

Scientists at LBMC have explored this situation experimentally by culturing yeast cells for several days and nights while changing their culture medium every three hours (about the time one cell needs to produce a daughter cell). This way, cells were forced to divide in alternating normal and stressful conditions. Each of these cells were defective for a specific gene, which allowed the team to apply a deep-sequencing method and detect genes that controlled proliferation in conidtions of repeated stress. Strikingly, many of these genes were not previously associated to the stress that was applied, showing that cells perceive the dynamics of their environment via mechanisms that were not suspected so far.

These results are fundamental to understand the timing of cellular adaptation and also how natural selection of mutations takes place in rapidly-changing environments.

Reference: Genomics of cellular proliferation in periodic environmental fluctuations, Salignon J, Richard M, Fulcrand E, Duplus-Bottin H and Yvert G. Mol Syst Biol. (2018) 14:e7823. DOI 10.15252/msb.20177823

Figure:
Healthy cells were mixed with cells harbouring a specific gene defect, and this population was cultured in normal condition (blue), continuously-stressful condition (yellow), and in repeated stress (dashed line). Mutant cells become rapidly predominant in condition of repeated stress.

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