Optogenetic Droplets: Using Light to Control Nucleoplasmic Phase Separation

核小体（NBs）是普遍存在的无膜结构，在基因调控中起着重要但鲜为人知的作用。NBs局部增加参与染色质重塑、转录起始和RNA加工的分子浓度。尽管它们具有重要的功能和数十年的研究，但我们缺乏对NB组装的定量、机制理解。了解控制NB组装和性质的生物物理规则是阐明其功能的关键。

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.