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Understanding how the function of biomolecular condensates scales with size

Mammalian cells are highly organized and comprise numerous membraneless biomolecular condensates with essential functions. Condensates vary in size at different levels: biomolecular condensates range from micrometer scale (e.g., nucleolus, splicing speckle) to nanometer scale (e.g., signaling puncta, transcription foci); the size of a given biomolecular condensate can be highly dynamic in live cells; most micrometer-scale condensates are not homogeneous but comprised of several nanometer-scale structures that undertake specific functions.

A variety of evidence suggests that the functions of biomolecular condensates may be related to their size. Theoretical studies and computer simulations of colloidal and metabolons have shown that small-number systems have many differences from their large-scale counterparts including phase transition patterns, surface tension, and functional behaviors. At the cell level, my previous studies on nucleolar ultrastructure have also provided some clues to the link between condensate size and function. However, it is still unclear whether the biomolecular condensates with different sizes have different properties and, in general, how biomolecular condensate functions scale with size.

My project aims to understand how the function of biomolecular condensates scales with size. From in vitro engineered systems to in vivo signaling pathways, I will study the size and ultrastructure of biomolecular condensates, investigate the relationships between their size and properties, and ultimately understand how their function is linked to their size. This project will give insights into the functional regulation of biomolecular condensates and provide practical information in both condensate research and engineering.

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