Descrizione del progetto
Uno studio potrebbe portare alla luce nuove informazioni sulla separazione di fase
Le cellule viventi fanno affidamento sulla compartimentazione di migliaia di molecole differenti e sulle loro reazioni chimiche. Molti compartimenti cellulari si costituiscono tramite la separazione di fase di eteropolimeri controllata da interazioni sequenza-specifiche, alimentando ciò che provoca un allontanamento delle reazioni dall’equilibrio. Il progetto FuelledLife, finanziato dall’UE, elaborerà una teoria per spiegare in che modo le separazioni di fase nelle cellule viventi danno origine a compartimenti distinti, in cui si verificano processi evolutivi, quali la selezione e la replicazione di biomolecole. Questo tipo di teoria potrebbe approfondire la nostra comprensione di come la separazione di fase di condensati di proteine riesca a regolare i processi biochimici in organismi multicellulari. Inoltre, potrebbe contribuire a chiarire il ruolo della separazione di fase all’origine della vita e, in particolare, svelare perché gli organismi moderni sfruttano una serie ristretta di compartimenti intracellulari.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
86159 Augsburg
Germania