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Selection and Regulation of Compartments by Fuel-driven Phase Separation

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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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2020-STG

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Host institution

UNIVERSITAET AUGSBURG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 498 852,00
Address
UNIVERSITAETSSTRASSE 2
86159 Augsburg
Germany

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Region
Bayern Schwaben Augsburg, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 498 852,00

Beneficiaries (1)

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