Optogenetic Droplets: Using Light to Control Nucleoplasmic Phase Separation

光遗传学液滴：利用光控制核质相分离

• 批准号: 9764304
• 负责人: Clifford P Brangwynne
• 金额: $ 22.6万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764304
• 关键词: Affinity; Architecture; Behavior; Biological Process; Biophysics; Cell Nucleolus; Cell Nucleus; Cells; Collaborations; Cultured Cells; Custom; Data; Dependence; Future; Gel; Gene Expression Regulation; Genes; Genome; Genomics; Health; Human; Human Cell Line; Hybrids; Investigative Techniques; Kinetics; Light; Link; Liquid substance; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Membrane; Nuclear; Optics; Organelles; Phase; Phase Transition; Play; Positioning Attribute; Property; Proteins; RNA; RNA Processing; Research Personnel; Role; Solid; Specificity; Structure; System; Technology; Testing; Theoretical model; Time; Transcription Initiation; Work; chromatin remodeling; genetic information; high throughput screening; insight; new technology; optogenetics; particle; programs; protein protein interaction; recruit; spatiotemporal; tissue/cell culture; tool; viscoelasticity

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.

核体（NB）是普遍存在的无膜结构，在基因调控中发挥着重要但人们知之甚少的作用。 NB 局部增加参与染色质重塑、转录起始和 RNA 加工的分子浓度。尽管它们具有重要的功能，并且经过了数十年的研究，但我们对 NB 组装缺乏定量、机制的理解。了解控制 NB 组装和特性的生物物理规则是阐明其功能的关键。 我们的小组率先提出了纳米粒子是通过相变聚集的液相液滴的概念。在这里，我们将建立在这个框架的基础上，并通过开发一种利用光控制核质相变的新技术来测试它。该技术将能够对纳米粒子的组装及其粘弹性特性进行精确的时空控制，并测试其对组成、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 NB，无论是在这些特定目标中，还是在 4D 核组计划的未来合作中。