权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Biophysics of Phase Separation in Protein-RNA Systems

蛋白质-RNA 系统中相分离的生物物理学

基本信息

批准号：
1818385
负责人：
Ashok Deniz
金额：
$ 71.3万
依托单位：
The Scripps Research Institute
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1818385&HistoricalAwards=false
关键词：
Biophysics Phase Separation Protein RNA

项目摘要

The project will develop and use novel tools to study how cellular materials are organized to facilitate chemical and biological functions that support life, while integrating broader impacts in teaching, training and outreach. The biology of humans and other organisms is critically dependent on interactions and chemistry of a host of cellular molecules. A key mechanism that underlies these correct interactions in a huge background of other molecules is the selective organization of molecules into different compartments. Indeed, cellular compartmentalization by a surrounding membrane has been studied in detail for decades. In contrast, another type of cellular compartment that lacks a membrane is common but less well-studied. These membraneless or "droplet" organelles are spontaneously formed by a phase transition (referred to as liquid-liquid phase separation, a process similar to oil-in-water droplet formation). In this project, novel methods to address unfilled gaps in our understanding of the physical principles underlying this process will be developed. The work is expected to result in new tools, insights and predictive principles that are broadly applicable in cell biology. The project will also integrate broader impacts in teaching, training and outreach, and aim to broaden participation in science. The work will be used as an excellent training ground for students in performing interdisciplinary research in a cutting-edge and timely area of research. The multidisciplinary nature of the research will also facilitate enhancement of graduate student curriculum, as well as outreach and communication of the research area to the broader community.Several membraneless organelles in cells contain proteins and RNA, both cellular macromolecules that are involved in a wide range of cellular processes. Understanding how molecular-level structure and interactions of these molecules link to the biophysics of droplet formation and membraneless organelles continues to pose challenges. The project will develop and use a combination of novel single-molecule and ensemble methods to study a series of important questions in this area. Single-molecule methods can provide access to critical information that is normally hidden by averaging over a large number of molecules. A method will be developed to probe size and conformational distributions in droplets smaller than typically detectable currently, by use of multicolor single-molecule detection. Another method will be developed to probe intermolecular interactions and conformational properties using single-molecule and chemical biology tools. These new tools and existing methods will be used to probe the determinants of complex phase transitions, non-equilibrium substructure formation and conformational patterning of protein-RNA droplets. The project is expected to reveal new insight in these aspects of cellular phase transitions and their functional consequenceThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目将开发和使用新的工具来研究细胞材料是如何组织起来的，以促进支持生命的化学和生物功能，同时在教学、培训和推广方面产生更广泛的影响。人类和其他生物的生物学严重依赖于细胞分子的相互作用和化学反应。在其他分子的巨大背景下，这些正确相互作用的一个关键机制是分子选择性地组织到不同的隔室中。实际上，细胞被周围的膜区隔化已经被详细研究了几十年。相比之下，另一种没有膜的细胞隔室很常见，但研究得较少。这些无膜或“液滴”细胞器是由相变自发形成的（称为液-液相分离，类似于油-水滴形成的过程）。在这个项目中，将开发新的方法来解决我们对这一过程背后的物理原理的理解中未填补的空白。这项工作有望产生新的工具、见解和预测原则，广泛应用于细胞生物学。该项目还将在教学、培训和推广方面整合更广泛的影响，并旨在扩大对科学的参与。这项工作将被用作学生在一个前沿和及时的研究领域进行跨学科研究的优秀训练基地。这项研究的多学科性质，亦有助加强研究生课程，以及扩大研究领域与更广泛社区的联系和交流。细胞中的几种无膜细胞器含有蛋白质和RNA，这两种细胞大分子都参与了广泛的细胞过程。了解这些分子的分子水平结构和相互作用如何与液滴形成和无膜细胞器的生物物理学联系起来仍然是一个挑战。该项目将开发和使用新的单分子和集成方法的组合来研究该领域的一系列重要问题。单分子方法可以提供获取关键信息的途径，而这些信息通常是通过对大量分子进行平均来隐藏的。我们将开发一种方法，通过使用多色单分子检测来探测比目前通常可检测的更小的液滴的大小和构象分布。将开发另一种方法，利用单分子和化学生物学工具来探测分子间相互作用和构象性质。这些新工具和现有方法将用于探测复杂相变的决定因素，非平衡亚结构的形成和蛋白质- rna液滴的构象模式。该项目有望揭示细胞相变及其功能后果方面的新见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。