Section: New Results

Effects of repeated osmotic stress on gene expression and growth: from cell-to-cell variability to cellular individuality in the budding yeast Saccharomyces cerevisiae

Participants : Grégory Batt, Ewen Corre, Pascal Hersen, Artémis Llamosi.

When shifted to a stressful environment, cells are capable of complex response and adaptations. Although the cellular response to a single stress has been studied in great detail, very little is known when it comes to dynamically fluctuating stressful environments. In addition, in the context of stress response, the role of cell-to-cell variability in cellular processes and more specifically in gene expression is still unclear.

In his PhD thesis [3] , Artémis Llamosi uses a systems and synthetic biology approach to investigate osmotic stress in S. cerevisiae at the single cell level. Combining microfluidics, fluorescent microscopy and advanced image analysis, we are able to subject cells to precise fluctuating osmolarity and monitor single-cell temporal response.

While much previous research in gene expression heterogeneity focused on its stochastic aspect, we consider here long-lasting differences between cells regarding expression kinetics. Using population models and state-of-the-art statistical analysis, we manage to represent both population and single-cell dynamics in a single concise modelling framework. This quantitative approach capturing stable individuality in gene expression dynamics can define a form of non-genetic cellular identity.

To improve our understanding of the biological interpretation of such identity, we investigate the relation between single-cell specificities in their gene expression with their phenotype and micro-environment. We then take a lineage based perspective and find this form of identity to be partially inherited.

Understanding the evolutionary consequences of inheritable non-genetic cellular identity requires a better knowledge of the impact of fluctuating stress on cell proliferation. Dissecting quantitatively the consequences of repeated stress on cell-cycle and growth gives us an overview of the energetic and temporal consequences of repeated stress. At last, technical and theoretical developments needed to carry this investigation further are presented.