Project description
Study could reveal new insight into phase separation
Living cells rely on the compartmentalisation of thousands of different molecules and their chemical reactions. Many cellular compartments form by phase separation of heteropolymers controlled by sequence-specific interactions and fuel that drives reactions away from equilibrium. The EU-funded FuelledLife project will develop a theory to explain how phase separations in living cells give rise to distinct compartments, in which evolutionary processes, such as the selection and replication of biomolecules, can take place. Such a theory would deepen our understanding of how phase separation of protein condensates can regulate biochemical processes in multicellular organisms. Furthermore, it could elucidate the role of phase separation at the origin of life, and in particular, reveal why modern organisms make use of a restricted set of intracellular compartments.
Objective
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.
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Funding Scheme
ERC-STG - Starting GrantHost institution
86159 Augsburg
Germany