Marina Garcia-Jove Navarro (Dept of Chemistry, ENS, Paris). Biophysics Seminar ESPCI-ENS

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30 March 13:00 » 14:00 — ENS, Conf IV, 2nd floor

Building phase-separated RNA-protein compartments in mammalian cells to study membrane-less organelles

Membrane-less organelles are ubiquitous intracellular compartments that localize and regulate complex biological processes without being surrounded by a boundary structure. They have been described as key regulators of RNA processing, DNA damage response and signal transduction; as they have been associated with neurodegenerative diseases and cancer. Interestingly, the general assembly model suggests that these micrometric compartments generate by a phase transition driven by multivalent weak interactions between biomolecules in the dilute state that demix into highly-concentrated liquid condensates. Numerous in vitro approaches have validated this self-assembly model, while advances in microscopy and high-throughput quantitative analysis expand the diversity of known endogenous membrane-less organelles. Yet, the dissection of the biophysical mechanisms of the dynamics and assembly of these condensates within living cells, and moreover, how it may affect their function, remain challenges for current approaches. We have developed a synthetic biology approach based on a versatile and modular protein scaffold that (i) self-assembles into micrometer-sized condensates in the cytoplasm of the cell in a concentration-dependent or stimuli-triggered manner and (ii) co-segregates endogenous components upon incorporation of specific design elements. Such a bottom-up approach is an interesting tool to assess the impact of parameters such as multivalency, affinity, composition, etc., on the self-assembly process as well as on condensate morphology and aging, but also to shed light on the spatiotemporal regulation of their formation and functions within the cell.

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