Gauging how the plasticity of cellular organizations dictates growth, death and adaptation in single bacterial cells

项目总结/摘要 细菌在不同的环境中经历戏剧性的细胞重组。了解非遗传的， 细胞组织的可逆可塑性对于阐明整个细胞水平的存活算法是至关重要的， 细菌的生长、适应和感染，在对抗病原体方面具有生物医学意义， 能适应各种环境并耐受人体内的抗生素。细胞空间里充斥着 生物分子却组织良好。然而，我们仍然缺乏对细胞空间是如何 有组织地支配细胞尺度的行为、生理和健康。我实验室的长期目标是 描述了细胞尺度的生命如何从生物分子及其相互作用中出现的基本原理。在 未来五年，我们将通过衡量蜂窝组织的关键功能如何互连来实现这一目标 与细菌细胞的生理状态和适应性，在模式生物如E.大肠杆菌和人类 病原体如铜绿假单胞菌。 细胞的组织通过物理，化学和生物学的结合与其生理状态相联系。 生物过程。我们将尝试通过检验两个基本假设来理清这种复杂性 我们的初步观察表明：（1）膜房地产假说-细胞质 细胞膜上充满了蛋白质，细胞需要微调蛋白质的密度、组成和结构。 组织的膜蛋白优化细胞健身，和（2）细胞盈余假说- 核心生物合成机器有一个多余的量，不利于稳态增长，而是 有利于适应新环境。为了更好地测试这些想法，我们将量化和操纵 膜蛋白的密度、组成和空间组织以及核心生物合成的丰度 机器，并检查它们对生理状态的影响，如生长，适应和细胞死亡。我们将 使用这些结果来测试物理模型，通过与 膜物理和操作物理的理论家。这些任务需要在定量和定量两方面的专业知识 实验和建模。我们实验室在生物物理学、生物工程学和分子生物学方面的经验 我们在一个独特的位置，以执行研究和促进跨领域的合作和互动。我们也 计划发布并与科学家分享在整个研究过程中产生的新工具和数据集， 社区，如微流体装置，图像分析软件和蛋白质物理数据库， 特性.无论这些假设是否会得到验证，这些项目的结果都可以帮助我们建立细胞间的桥梁。 组织和生理学，并了解更好的细胞适应，知识的分支，可以 延伸到研究其他高等生物。

Project Summary/Abstract Bacteria undergo dramatic cellular re-organizations in different environments. Understanding the non-genetic, reversible plasticity of cellular organization is crucial to unraveling the whole-cell level algorithm of survival, growth, adaptation, and infection of bacteria, with biomedical significance in combating pathogens that can adapt to various niches and tolerate antibiotics in the human body. Cellular space is incredibly crowded with biomolecules yet well-organized. However, we still lack a precise understanding of how cellular space is organized to dictate cellular scale behaviors, physiology, and fitness. The long-term goal of my lab is to delineate basic principles of how life at the cellular scale emerges from biomolecules and their interactions. In the next five years, we will pursue this goal by gauging how key features of cellular organizations interconnect with physiological states and fitness in bacterial cells, in model organisms such as E. coli, and human pathogens such as P. aeruginosa. The organization of the cell connects to its physiological state via a combination of physical, chemical, and biological processes. We will try to disentangle this complexity by testing two fundamental hypotheses suggested by our preliminary observations: (1) the membrane real-estate hypothesis – the cytoplasmic membrane is so packed with proteins that the cell needs to fine-tune the density, composition, and organization of the membrane proteins for optimizing cell fitness, and (2) the cellular surplus hypothesis – the core biosynthetic machines have an excess amount that does not benefit steady-state growth, but rather is beneficial for adaptation to a new environment. To better test these ideas, we will quantify and manipulate the density, composition, and spatial organization of membrane proteins and the abundance of core biosynthetic machines and examine their effects on physiological states such as growth, adaptation, and cell death. We will use these results to test physical models that render possible optimality principles by collaborating with theorists in membrane physics and operations physics. These tasks require expertise in both quantitative experiments and modeling. Our lab’s experience in biophysics, bioengineering, and molecular biology will set us in a unique position to perform the research and foster cross-field collaborations and interactions. We also plan to publish and share new tools and datasets to be yielded throughout the research with the scientific community, such as microfluidic devices, image analysis software, and databases of protein physical properties. Whether these hypotheses will be verified, outcomes from these projects can help us bridge cellular organization and physiology and understand better cellular adaptation, a branch of knowledge that can be extended to studying other higher organisms.