Biophysical mechanisms driving spatial organization in bacterial cells

Normal.dotm 0 0 1 三百零七 1754年 斯坦福大学 14. 3. 2154 12.0 0 错误 18磅 18磅 0 0 错误 错误 错误 /*样式定义*/ Table.MsoNormalTable {mso-style-name：“正常表”； Mso-tstyle-rowband-Size：0； Mso-tstyle-colband-Size：0； MSO-Style-noshow：是的； MSO风格-家长：“”； MSO-PADDING-ALT：0in 5.4pt 0in 5.4pt； MSO-Para-March：0in； MSO-对边距-底部：.0001pt； MSO-分页：寡妇-孤儿； 字体大小：12.0pt； Font-Family：“Times New Roman”； MSO-ASCII-FONT-家族：寒武纪； MSO-ASCII-主题-字体：小调-拉丁语； MSO-FARAAST-FONT-FAMILY：“Times New Roman”； MSO-Fareast-Theme-Font：Minor-Fareast； MSO-HANSI-FONT-家族：寒武纪； MSO-HANSI-TIME-FONT：小调-拉丁语；} 活细胞被分成称为细胞器的功能隔间。在真核生物中，膜在细胞器和细胞质之间建立了扩散屏障，因此每个隔室都保持着不同的生化成分，这是为其特定的功能量身定做的。膜结合细胞器的结构和功能背后的生物物理机制被很好地理解。然而，细胞也含有不被膜包裹的细胞器。例如，应激颗粒、P小体和核仁属于一类称为“细胞体”的无膜细胞器。这些小体由局部浓缩的蛋白质和核酸组成，它们与周围的细胞质或核质快速交换。最近的证据表明，细胞体是通过液-液相分离的方式聚集在一起的，在此过程中，可溶分子从细胞质(或核质)凝聚形成浓缩的液状细胞器。我在核仁方面的博士后研究工作有助于将相分离定义为细胞内组织的一种新机制。核仁是负责核糖体生物发生的大型细胞体。 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细胞器，相分离可以为这一生命领域的空间和功能组织提供一种替代机制。我的实验室将使用大肠杆菌中的转录焦点来探索这一想法。转录焦点是一簇RNA聚合酶，看起来像是核仁的结构和功能类似物。因此，我假设Tf是细胞体，它们(I)通过相分离聚集在一起，(Ii)功能是加速核糖体生物。

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