Molecular Mechanisms and Biochemical Circuits for Adaptation in Biological Systems

生物系统适应的分子机制和生化回路

基本信息

批准号：
10687856
负责人：
Yuhai Tu
金额：
$ 27.99万
依托单位：
IBM THOMAS J. WATSON RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

项目摘要

Project Summary Adaptation is one of the most important and defining properties of all biological systems ranging from a single cell to multi-cellular organisms to populations of interacting species. Adaptation allows living systems to adjust themselves in response to environmental changes and stresses to maintain their normal functions. Therefore, the ability to adapt is crucial for the health and fitness of living systems from human to a single cell. For adaptation at the cellular level, much progresses have been made in identifying key molecular components relevant for adaptation and in measuring the adaptive input-output responses in individual systems. However, despite these advances, many fundamental questions on cellular level adaptation remain unresolved. What are the general system-level molecular mechanisms for adaptation to different types of (chemical and mechanical) stimuli in living cells? Are there any universal design principles governing the underlying biochemical pathways (circuits) that are responsible for the vast variety of adaptive behaviors in cells? In this proposed program, we aim to address these questions broadly to bridge the gap between molecular interactions and system-level adaptation behaviors by using an integrated approach that combines theoretical analysis and computational modeling with quantitative experiments from our experimental collaborators' labs. We plan to study three representative cellular systems: 1) adaptation to chemical signals in bacterium cells (Escherichia coli); 2) adaptation to mechanical signals in bacterial flagellar motor (BFM); 3) adaptation to odor stimuli in olfactory sensory neurons (OSN). In each of these systems, we will develop a system-level model based on known molecular components and their interactions. These system-level models will allow us to verify/falsify different possible molecular mechanisms (hypotheses) against the system level input-output measurements. By comparing the molecular mechanisms for adaptation in these diverse systems, we aim to uncover general features (design principles) in the underlying biochemical pathways (circuits), which should provide a general framework for understanding other cellular adaptation systems such as metal homeostasis, response to osmotic pressure, chemotaxis in Eukaryotic cells, and adaptations of sensory neurons in different sensory modalities.

项目摘要适应是所有生物系统的最重要，最定义的特性之一细胞到多细胞生物到相互作用物种的种群。适应允许生活系统调整响应环境变化和压力，以维持其正常功能。所以，适应能力对于从人到单个细胞的生活系统的健康和适应性至关重要。为了在细胞水平上适应，在识别关键分子成分方面已经取得了很多进展与适应和测量单个系统中的自适应输入输出响应有关。然而，尽管有这些进展，但许多有关细胞水平适应的基本问题仍未解决。什么是适应不同类型（化学和机械）的一般系统级分子机制活细胞的刺激？是否有任何统治基础生化途径的通用设计原则（电路）负责细胞中各种各样的适应性行为？在此提议的计划中，我们旨在广泛解决这些问题，以弥合分子之间的差距相互作用和系统级适应行为通过使用结合理论的集成方法通过我们实验合作者实验室的定量实验进行分析和计算建模。我们计划研究三个代表性的细胞系统：1）对细菌细胞中化学信号的适应（大肠杆菌）； 2）适应细菌鞭毛电动机（BFM）中的机械信号； 3）适应气味嗅觉感觉神经元（OSN）中的刺激。在每个系统中，我们将开发一个系统级模型基于已知的分子成分及其相互作用。这些系统级的模型将使我们能够针对系统级别输入输出验证/伪造不同可能的分子机制（假设）测量。通过比较这些不同系统中适应的分子机制，我们的目标是发现基础生化途径（电路）中的一般特征（设计原理），该途径应提供一个通用框架，以了解其他细胞适应系统，例如金属稳态，对渗透压的反应，真核细胞中的趋化性以及不同的感觉神经元的适应感官方式。