Optogenetic Droplets: Using Light to Control Nucleoplasmic Phase Separation

核体(NBS)是普遍存在的无膜结构，在基因调控中发挥着重要但鲜为人知的作用。NBS局部增加了参与染色质重塑、转录启动和RNA加工的分子的浓度。尽管它们在功能上很重要，而且经过几十年的研究，我们对NB组装缺乏定量的、机械的理解。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。 我们小组率先提出了NBS是通过相变组装的液态液滴的概念。在这里，我们将在这个框架的基础上，通过开发一种利用光来控制核质相变的新技术来对其进行测试。这项技术将能够对NBS的组装及其粘弹性特性进行精确的时空控制，并测试对组成、功能和基因组结构的影响。我们的团队处于独特的地位，可以开发这项令人兴奋的技术，并利用它来研究NBS，无论是在这些特定的目标上，还是在未来4D基因组计划的合作中都是如此。

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.