Metabolic constraints determining cell states in space, and over time
Investigator & Wellcome Trust –DBT IA fellow InStem, Bangalore
Our overarching goal is to understand rules governing metabolic information flow at systems and molecular scales, and how they regulates different cell states. Genetically identical cells, even in constant environments, can form phenotypically heterogenous communities, with cells in different states. When spatially constrained, cells organize into groups exhibiting distinct patterns, forms, shapes and function. In well-mixed systems, groups of cells can exhibit synchronous behavior or oscillations, with distinct cell state outcomes. An underlying biochemical basis for how phenotypically heterogenous cell states emerge and spatially organize remains unclear. In this talk I will present our studies using S. cerevisiae, where we model and experimentally address how metabolic determinants are sufficient to determine the spatial self-organization of cells into specialized communities. These constraints control how cells with apparently impossible metabolic states can emerge and thrive, within spatial restraints. Using this approach, we experimentally identify a specific metabolite that is produced by cells, and show how the differential utilization of this metabolite can control the emergence of cells exhibiting metabolically distinct ‘non-permissible’ states. These data suggest biochemical frameworks to understand, predict and control how isogenic cells self-organize into specialized communities. Similary, in well mixed systems of S. cerevisiae exhibiting coupled metabolic and cell cycle oscillations, we combine coarse-grained models and experiments to determine how threshold amounts of a central metabolite can determine oscillations of groups of cells between quiescent and growing/dividing states.