Biophysical mechanisms driving spatial organization in bacterial cells

正常.dotm 0 0 1 307 1754斯坦福大学14 3 2154 12.0 0假 18分18分0 0 假假假 /* 样式定义 */table.MsoNormalTable {mso-style-name：“Table Normal”; mso-tstyle-rowband-size：0; mso-tstyle-colband-size：0; mso-style-noshow：yes; mso-style-parent：“"; mso-padding-alt：0in 5.4pt 0in 5.4pt; mso-para-margin：0in; mso-para-margin-bottom：.0001pt; mso-pagination：widow-orphan; font-size：12.0pt; font-family：“Times New Roman”; mso-asleep-font-family：Cambria; mso-asleep-theme-font：minor-latin; mso-fareast-font-family：“Times New Roman”; mso-fareast-theme-font：minor-fareast; mso-hansi-font-family：Cambria; mso-hansi-theme-font：minor-latin;}活细胞被分成称为细胞器的功能区室。在真核生物中，膜在细胞器和细胞质之间形成扩散屏障，使得每个隔室维持针对其特定功能定制的独特生化组成。 膜结合细胞器的结构和功能的生物物理机制是很好的理解。然而，细胞也含有不被膜包围的细胞器。 例如，应激颗粒、P体和核仁属于一类称为“细胞体”的无膜细胞器。这些小体由局部集中的蛋白质和核酸组成，它们与周围的细胞质或核质迅速交换。最近的证据表明，细胞体通过液-液相分离组装，在此期间，可溶性分子从细胞质（或核质）浓缩形成浓缩的液体样细胞器。我的博士后工作是关于核仁，一个负责核糖体生物合成的大细胞体，这有助于将相分离定义为细胞内组织的新机制。 在这里，我建议在一个新的生物学背景下研究这些概念：细菌。 由于原核生物通常缺乏膜结合的细胞器，相分离可以提供一个替代机制的空间和功能组织在这个领域的生活。我的实验室将利用E.杆菌转录灶是RNA聚合酶的簇，它们似乎是核仁的结构和功能类似物。因此，我假设TF是一种细胞体，（i）通过相分离组装，（ii）起加速核糖体生物降解的作用。

Normal.dotm 0 0 1 307 1754 Stanford University 14 3 2154 12.0 0 false 18 pt 18 pt 0 0 false false false /* Style Definitions */table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin;}Living cells are divided into functional compartments called organelles. In eukaryotes, membranes create a diffusion barrier between organelles and the cytoplasm, such that each compartment maintains a distinct biochemical composition that is tailored for its particular function. The biophysical mechanisms underlying the structure and function of membrane-bound organelles are well understood. However, cells also contain organelles that are not enclosed by membranes. For example, stress granules, P bodies and the nucleolus belong to a class of membraneless organelles called "cellular bodies". These bodies consist of local concentrations of proteins and nucleic acids that rapidly exchange with the surrounding cytoplasm or nucleoplasm. Recent evidence suggests that cellular bodies assemble by liquid-liquid phase separation, during which soluble molecules condense from the cytoplasm (or nucleoplasm) to form concentrated liquid-like organelles. My postdoctoral work on the nucleolus, a large cellular body responsible for ribosome biogenesis, was instrumental in defining phase separation as a new mechanism for intracellular organization. Here, I propose to investigate these concepts in a new biological context: bacteria. Since prokaryotes typically lack membrane-bound organelles, phase separation could provide an alternate mechanism for spatial and functional organization in this domain of life. My lab will explore this idea using transcription foci in E. coli. Transcription foci are clusters of RNA polymerase that appear to be structural and functional analogs of the nucleolus. Therefore, I hypothesize that TF are cellular bodies that (i) assemble by phase separation and (ii) function to accelerate ribosome biog