MICROCOSME combines computational and experimental approaches for the analysis, engineering, and control of the growth of micro-organisms. The team joins researchers from Inria Grenoble – Rhône-Alpes and the Laboratoire Interdisciplinaire de Physique at Université Grenoble Alpes (CNRS UMR 5588).
Microorganisms are found everywhere, in soils, in water, and in humans, where on average 1.3 bacterial cells are counted for every human cell. One of the defining characteristics of microorganisms is their capacity to grow and divide, that is, transform nutrients from the environment into new microbial cells. They multiply fast in permissive conditions (doubling every twenty minutes), slow in adverse conditions (doubling every few hours or days), or not at all in case of extreme stress. Understanding and controlling the dynamics of bacterial growth is vitally important in health, medicine, biotechnology, and food industries, for instance to halt the growth of pathogens or stimulate the growth of probiotics or industrial microorganisms.
The inside story
Microbial growth is essentially a multiscale phenomenon, in the sense that the macroscopic observable, growth of a microbial population, depends on various metabolic pathways and regulatory mechanisms operating at microscopic scales within the cells. Novel experimental technologies have provided an increasingly detailed and quantitative account of these pathways and regulatory mechanisms, including complex feedback mechanisms operating on different time-scales. Recent advances in genome engineering have used this knowledge to enable directed genetic modifications that turn microorganisms into microbial cell factories capable of producing a range of metabolites, peptides, and proteins of industrial and medical interest.
Despite these technological advances, many if not most fundamental questions on microbial growth remain open. For instance, growth of microorganisms requires the synthesis of different cellular components in a timely manner under resource constraints. How do cells coordinate the different intracellular growth processes and adjust bacterial growth rate to an ever-changing environment? How do they allocate limiting cellular machineries to these processes so as to grow optimally in permissive conditions or to survive in harmful environments? How do fluctuations lead to heterogeneous growth behaviour over a population? How can feedback control stabilize the composition of a synthetic community of microorganisms and optimize the production of a metabolite of interest?
Research in MICROCOSME
Research in MICROCOSME addresses these questions. The research program is organized around four axes depicted below, which make use of tools from mathematical modelling (stochastic and deterministic), dynamical systems analysis, control theory, genome and bioprocess engineering: