Optogenetic Droplets: Using Light to Control Nucleoplasmic Phase Separation

核小体（NB）是一种普遍存在的无膜结构，在基因调控中起着重要但知之甚少的作用。NB局部增加参与染色质重塑、转录起始和RNA加工的分子的浓度。尽管它们在功能上很重要，并且经过了几十年的研究，但我们对NB组装缺乏定量的、机械的理解。了解NB组装和性质的生物物理规则是阐明其功能的关键。 我们的团队开创了NB是通过相变组装的液相液滴的概念。在这里，我们将建立在这个框架，并测试它，通过开发一种新的技术，使用光来控制核质相变。该技术将能够精确时空控制NB的组装及其粘弹性，并测试其对组成、功能和基因组结构的影响。我们的团队具有独特的优势来开发这项令人兴奋的技术，并利用它来研究NB，无论是在这些特定目标中，还是在4D Nucleome计划中的未来合作中。

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.