INSPIRE: Minimal adaptive and replicating cell

INSPIRE：最小适应性和复制细胞

• 批准号: 1632756
• 负责人: Devarajan Thirumalai
• 金额: $ 100万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-03 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1632756&HistoricalAwards=false
• 关键词: INSPIRE; Minimal; adaptive; replicating; cell

This INSPIRE project is co-funded by the Chemistry of Life Processes Program in the Chemistry Division in the Directorate for Mathematical and Physical Sciences, the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences, the Physics of Living Systems Program in the Physics Division in the Directorate for Mathematical and Physical Sciences and the Office of Integrative Activities in the Directorate for Mathematical and Physical Sciences.The two fundamental characteristics of living systems are their ability to replicate with precision and adapt to changing environmental conditions. The discovery of the structure of DNA, the molecule that carries genetic information, provided only a framework for describing how the genetic code is copied. However, focusing on DNA in isolation does not provide insights into how the entire machinery, needed to sustain the viability of the cell, is conveyed from the mother to the daughter cell. This is accomplished by networks of other protein molecules that transmit information through chemical reactions both in the process of replication, cell division, and adaptation. How do theses individual molecular components interact and function in a system that is capable of replicating, adapting to changing environment, and operating robustly in noisy crowded milieu? What is the minimum level of complexity needed for a living cell to function? What sets the length scale of such a living system in terms of the molecular constituents? The goal is to develop a quantitative conceptual framework to answer these questions so that the ability to process signals, adapt, and replicate with high fidelity can be described using the laws of physics and chemistry and using a bacterium as a case study. The interdisciplinary approach to this research involves integrating physics, chemistry, and information theory concepts, and is expected to provide a versatile training ground for students and postdoctoral fellows with diverse backgrounds.In order to achieve the major objectives of the proposed research it is necessary to break new ground by creating new models and ideas coming from a variety of fields. An integrated approach will be developed by combining coarse-grained models of enzymatic reactions, ways of coupling feedback effects due to synthesis of small molecules and proteins, and accounting for non-equilibrium processes. These ideas will be used to explore the organization principles for adaptation to environmental fluctuations, cell size control, and competition between various factors that promote homeostasis. These new concepts will be used to provide a new framework on how a simple bacterium is versatile enough to respond to harsh environmental fluctuations (high salinity or osmolarity) and adapt in a noisy environment. Analyzing such behavior will require combining control theory and the underlying stochastic aspects of signal transmission achieved through chemical reaction networks. In addition, the key question of how cell shape and size (on the order of a micron) emerge will be explored based on the notion that they use feedback to maintain proteostasis and keep the concentrations of metabolites in check. The questions raised here are fundamental and even if answered partially could have far-reaching implications in our understanding of how living systems function. An overarching long term goal of these studies is to begin to provide the framework to eventually design and control macroscopic cell behavior in terms of its underlying components.

这个激发项目由数学和物理科学局的化学过程中的化学过程计划共同资助，分子生物物理学集群在生物学科学局的分子和细胞生物科学局中，在生物科学局中，在物理和物理科学局的物理局局长的物理系统局和数学专业局的董事会局长，该局的数学和局部数学专业局，科学。生活系统的两个基本特征是它们精确复制并适应不断变化的环境条件的能力。 DNA结构的发现，即带有遗传信息的分子，仅提供了描述遗传密码如何复制的框架。但是，专注于孤立的DNA并没有提供有关如何维持细胞可行性所需的整个机械的见解，从母亲传达到女儿细胞。这是通过其他蛋白质分子的网络来完成的，这些网络在复制，细胞分裂和适应过程中都通过化学反应传输信息。这些单个分子成分如何在能够复制，适应不断变化的环境并在嘈杂的拥挤环境中进行健壮的系统中的相互作用和功能？ 活细胞发挥作用所需的最低复杂性水平是多少？是什么根据分子成分设定了这种生活系统的长度尺度？目的是开发一个定量的概念框架来回答这些问题，以便可以使用物理和化学定律以及将细菌作为案例研究来处理信号，适应和复制的能力。这项研究的跨学科方法涉及整合物理，化学和信息理论概念，并有望为学生和具有不同背景的博士后研究员提供多功能的培训场。通过结合酶促反应的粗粒模型，由于小分子和蛋白质的合成以及对非平衡过程的耦合反馈效应的方式，将开发一种综合方法。这些想法将用于探索组织原则，以适应环境波动，细胞大小控制以及促进体内平衡的各种因素之间的竞争。 这些新概念将用于提供一个新的框架，以了解简单细菌如何用途足够多，以应对严峻的环境波动（高盐度或渗透率）并在嘈杂的环境中进行适应。 分析这种行为将需要结合控制理论和通过化学反应网络实现的信号传递的潜在随机方面。 此外，将基于他们使用反馈来维持蛋白质的观念并将代谢物的浓度保持检查的概念来探索细胞形状和大小（按微米的顺序）出现的关键问题。这里提出的问题是基本的，即使部分回答可能会对我们对生活系统的运作方式产生深远的影响。这些研究的总体长期目标是开始为最终设计和控制宏观细胞行为的框架提供其基本组件。