Nuclear bodies (NBs) are ubiquitous membrane-less structures that play important but poorly-understood roles in gene regulation. NBs locally increase the concentration of molecules involved in chromatin remodeling, transcription initiation, and RNA processing. Despite their functional importance, and decades of study, we lack a quantitative, mechanistic understanding of NB assembly. Understanding the biophysical rules governing NB assembly and properties is key to elucidating their function. Our group has pioneered the concept that NBs are liquid phase droplets that assemble through phase transitions. Here we will build on this framework, and test it, by developing a new technology that uses light to control nucleoplasmic phase transitions. This technology will enable precise spatiotemporal control of the assembly of NBs and their viscoelastic properties, as well as testing the impact on composition, function, and genome architecture. Our team is uniquely positioned to develop this exciting technology and exploit it to study NBs, both in these Specific Aims, as well as together in future collaborations within the 4D Nucleome Program.
Nuclear bodies are RNA/protein organelles that regulate the flow of genetic information, and are thus important for a wide range of biological processes. Our understanding of the biophysical rules governing their assembly and function has been hampered by a lack of tools for precisely perturbing them. In this proposal, we will develop a cutting-edge technology to control nuclear body assembly and properties with light, exploiting it first to study the nucleolus - the largest and prototypical nuclear body, which is dysregulated in various cancers.
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