CAREER: ATP-driven Spatial Regulation of a Biomolecular Condensate in Bacteria

今天大气中的二氧化碳含量比过去80万年中的任何时候都要高，因此，了解碳固定机制变得非常重要。全球几乎一半的碳修复是由细菌完成的，细菌将二氧化碳固定到完全由蛋白质构成的细胞器中。尽管它们对全球碳循环很重要，但在细胞中如何组织羧基体尚不清楚。本研究将阐明羧基体组织的机制，以了解这种重要的细胞器如何在细胞群中维持。对羧基体组织的基本生物学机制的理解将为利用它们进行合成生物学应用提供一种手段。该项目将进一步推动美国国家科学基金会的使命，即通过改善自然碳固定来扩大科学和工程研究的潜力，并通过让公众了解细菌的功能如何具有全球影响，对教育、吸引公众和提高科学素养具有广泛的影响。细胞器传统上被认为是脂质结合的，仅限于真核细胞。现在认识到无膜细胞器存在于所有类型的细胞中。最近发现的一种形成无膜细胞器的方法是液-液相分离，其中蛋白质凝结成液滴。关于无膜细胞器是如何在细胞中组织起来的，我们所知甚少。最近的几项研究表明，羧基体具有类似液体的性质——这是我们对这些固定碳细胞器的理解的一个范式转变。在蓝藻长聚球菌中，羧酸体沿细胞长度均匀分布。项目团队最近确定了负责维持羧基体分布的系统，但其机制仍然未知。这项研究将有助于首次了解液体样细胞器在细菌中的空间组织机制。该项目由生物科学理事会分子和细胞生物科学部细胞动力学、功能和分子生物物理集群联合资助。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。

Atmospheric carbon dioxide levels are higher today than at any point in the past 800,000 years, therefore, understanding carbon fixation mechanisms has become very important. Almost half of global carbon remediation is performed by bacteria that package the machinery required to fix carbon dioxide into organelles made entirely of protein called carboxysomes. Despite their importance to the global carbon cycle, how a carboxysome is organized in the cell is unclear. This research will elucidate the mechanisms of carboxysome organization to understand how this vital organelle is maintained in a cell population. An understanding of the basic biological mechanisms by which carboxysomes are organized will provide a means to utilize them for synthetic biology applications. This project will further NSF’s mission of expanding science and engineering research potential by improving natural carbon fixation and has broad impacts on education, engaging the public, and increasing scientific literacy by giving the public an appreciation for how bacterial function can have global implications.Organelles are traditionally thought of as lipid bound and restricted to eukaryotic cells. It is now appreciated that membraneless organelles are present in all cell types. A recently identified way to form a membraneless organelle is by Liquid-Liquid Phase Separation, where proteins condense into droplets. Little is known about how membraneless organelles are organized in a cell. Several recent studies suggest the carboxysome has liquid-like properties - a paradigm shift in our understanding of these carbon-fixing organelles. In the cyanobacterium Synechococcus elongatus, carboxysomes are evenly spaced along the cell length. The project team recently identified the system responsible for the maintenance of carboxysome distribution, but the mechanism remains unknown. This research will contribute the first mechanistic understanding of how liquid-like organelles are spatially organized in bacteria.This project is jointly funded by the Cellular Dynamics and Function and Molecular Biophysics Clusters, Division of Molecular and Cellular Biosciences, Directorate for Biological Sciences.This 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.