Description du projet
Une étude pourrait dévoiler de nouvelles informations sur la séparation de phase
Les cellules vivantes s’appuient sur la compartimentation de milliers de différentes molécules et leurs réactions chimiques. De nombreux compartiments cellulaires se forment via la séparation de phase d’hétéropolymères, contrôlée par des interactions et des carburants spécifiques à la séquence qui éloignent les réactions de leur point d’équilibre. Le projet FuelledLife, financé par l’UE, entend développer une théorie visant à expliquer la manière dont les séparations de phase au sein des cellules vivantes donnent naissance à des compartiments distincts, à l’intérieur desquels des processus évolutifs tels que la sélection et la réplication de biomolécules peuvent survenir. Une telle théorie permettrait d’approfondir notre compréhension de la manière dont la séparation de phase des condensats de protéines est susceptible de réguler des processus biochimiques dans des organismes multicellulaires. En outre, elle permettrait d’élucider le rôle de la séparation de phase à l’origine de la vie, et plus particulièrement, de révéler pourquoi on retrouve un ensemble limité de compartiments intracellulaires chez les organismes modernes.
Objectif
Living cells rely on the compartmentalisation of thousands of different molecules and their chemical reactions. Remarkably, many of such compartments form by phase separation of heteropolymers controlled by sequence-specific interactions and fuel that drives reactions away from equilibrium. If we knew how such polymers with sequence-specific interactions evolve and compartmentalise in fuel-driven multi-component mixtures, we would better understand the role of phase separation in living cells and how synthetic or prebiotic cells emerge.
I aim to study how fuel-driven phase separation can drive the selection and replication of hetero-polymers with sequence-specific interactions, the control of their chemical reactions and the emergence and selection of different compartments. My team and I will develop a theory for phase separation and chemical reactions in multi-component mixtures driven away from equilibrium by irreversible, fuel-driven reactions. This theory will provide a link between phenomena on the compartment scale and coarse-grained properties of sequences. First, we will use this theory to study how compartments control biochemical reactions, and how this control is determined by sequence. Second, we will investigate how sequences are selected, replicated and evolve under cyclic, non-equilibrium conditions. Third, we will use our theory to unravel how fuel-driven chemical reactions regulate formation and division of compartments, and affect selection of different compartments within a population. Our theoretical studies will elucidate the physical mechanisms and conditions which will be experimentally scrutinised by our collaborators.
Our results will let us understand how living cells regulate phase separation, like the formation of stress granules by selecting RNA. Moreover, our results will elucidate the role of phase separation for the emergence of life by determining the prerequisites of a protocell to divide, replicate and undergo selection.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
86159 Augsburg
Allemagne