eVOLve

Regulation of cell volume is a central aspect of the biology of living eukaryotic systems. In metazoa, it contributes to the overall size and shape of an organism and plays an important role in the development and architecture of tissues with dedicated functions. At the single-cell level, volume and surface area not only define how cells sense external stimuli and interact with their environment but also dictate their intracellular chemistry and organisation. Cell volume is a complex trait that is regulated by both genetic and environmental components. It has an impact on a host of processes, ranging from cytoskeletal dynamics to the scaling of global transcription rates, and it may be one of the most pleiotropic parameters in cell biology. Nevertheless, we have a surprisingly limited understanding of the way cell volume is controlled and its complex influence on cellular function, in particular due to the difficulty of assessing cell size accurately. Intriguingly, one key area that has remained largely unexplored is how cell volume may be modulated during evolution as part of the long-term cellular response to specific chemical and physical environments. We therefore propose to depart from the study of the mechanisms underlying short-term size homeostasis to investigate the interplay between cell volume and adaptation. To this end, we will use fission yeast as a model system and combine experimental evolution approaches, novel methods for accurate volume measurement, and in-depth genomic studies of natural isolates. First, we will evaluate whether volume changes are an important and recurring consequence of cellular adaptation, and conversely whether applying a selection pressure on cell size favours enhanced growth in adverse conditions. We will then assess the mechanisms by which these volume alterations occur and study how they impact cell proliferation. Next, we will determine whether the initial volume of cells modulates their adaptation dynamics and evolutionary trajectories in challenging environments. We will also ascertain the trade-offs that changes in cell size may impose, providing new insights into the way this parameter may have been set during evolution. Finally, we will probe the link between volume and adaptation by investigating natural variation in closely related fission yeast lineages, taking advantage of advanced genomic analyses. Collectively, the different aims of this multidisciplinary project build on the specific expertise of the two teams to bring a new understanding to the intricate relationship between cell size and evolution.