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10 July

Erez Braun The living cell as a sloppy dynamical system

10h30 à 12h

Le séminaire de Erez Braun (Department of Physics & Network Biology Research Laboratories, Technion) aura lieu dans l’amphi Urbain ESPCI, 10 Rue Vauquelin, Escalier N

Sloppy is a term used to describe a large class of models in physics and biology, exhibiting large uncertainty in their parameters when fit to data. I argue that the living cell itself is a sloppy system; namely, it does not fix its own kinetic parameters but rather utilizes this freedom to adapt. Indeed, biological cells present a paradox, in that they show simultaneous stability and flexibility, allowing them to adapt to new environments and to evolve over time. The emergence of stable cell states depends on genotype-to-phenotype associations, which essentially reflect the organization of gene regulatory modes. These in turn, determine the protein content of a cell—the primary determinant of its morphology, metabolism and function. However, the protein content fluctuates even among genetically identical cells in a population grown in well-mixed environments, resulting in broad distributions. We show that protein distributions measured under a wide range of biological realizations, have a universal shape, independent of the underlying biological specificity. Thus, cell-to-cell fluctuations do not reflect microscopic noise. We also show that the population-average protein dynamics exhibit slow collective modes that do not reflect specific biological functionality. These results suggest that due to its sloppy characteristics, the content of each individual protein in the living cell is not by itself a relevant variable. How the protein degrees of freedom are utilized effectively to support the cell’s functionality is therefore an open question. Our experiments suggest that the emergence of stable cell states should be understood by searching the relevant variables in the form of collective modes.