INSPIRE: Minimal adaptive and replicating cell
INSPIRE:最小适应性和复制细胞
基本信息
- 批准号:1632756
- 负责人:
- 金额:$ 100万
- 依托单位:
- 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:
- 关键词:
项目摘要
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.
该INSPIRE项目由数学和物理科学理事会化学部生命过程化学项目、生物科学理事会分子和细胞生物科学部分子生物物理学小组、生命系统物理学计划在物理司在数学和物理科学和综合活动办公室在生命系统的两个基本特征是精确复制和适应不断变化的环境条件的能力。携带遗传信息的分子DNA结构的发现,仅仅为描述遗传密码是如何复制的提供了一个框架。然而,关注孤立的DNA并不能深入了解维持细胞活力所需的整个机制如何从母体细胞传递到子细胞。这是由其他蛋白质分子网络完成的,这些蛋白质分子通过复制、细胞分裂和适应过程中的化学反应传递信息。在一个能够复制、适应不断变化的环境并在嘈杂拥挤的环境中稳健运行的系统中,这些单个分子组件是如何相互作用和发挥作用的? 一个活细胞发挥功能所需的最低复杂程度是多少?是什么决定了这样一个生命系统的分子组成长度?我们的目标是开发一个定量的概念框架来回答这些问题,以便使用物理和化学定律并使用细菌作为案例研究来描述处理信号,适应和高保真复制的能力。本研究采用物理学、化学、信息论的跨学科方法,为不同背景的学生和博士后研究员提供多功能的培养基地。为了实现本研究的主要目标,需要从各个领域创造新的模型和想法,开拓新的领域。一个综合的方法将开发相结合的粗粒度模型的酶促反应,由于小分子和蛋白质的合成耦合反馈效应的方式,并占非平衡过程。这些想法将用于探索适应环境波动,细胞大小控制和促进稳态的各种因素之间的竞争的组织原则。 这些新概念将用于提供一个新的框架,说明简单的细菌如何能够适应恶劣的环境波动(高盐度或渗透压)并适应嘈杂的环境。 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输的潜在随机方面。 此外,细胞形状和大小(微米级)如何出现的关键问题将基于它们使用反馈来维持蛋白质稳态并保持代谢物浓度的概念进行探索。这里提出的问题是根本性的,即使部分回答也可能对我们理解生命系统的功能产生深远的影响。这些研究的首要长期目标是开始提供框架,以最终设计和控制宏观细胞行为的基本组成部分。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Devarajan Thirumalai其他文献
Hydration of Magnesium is Required for Myosin VI Phosphate Release
- DOI:
10.1016/j.bpj.2017.11.1788 - 发表时间:
2018-02-02 - 期刊:
- 影响因子:
- 作者:
Mauro L. Mugnai;Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
TMAO and Solvent Exposed RNA Bases Stabilizes Unfolded State via Hydrogen Bonding
- DOI:
10.1016/j.bpj.2008.12.3009 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:
- 作者:
Samuel Cho;Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
Crowding Induced Conformational Switch
- DOI:
10.1016/j.bpj.2010.12.240 - 发表时间:
2011-02-02 - 期刊:
- 影响因子:
- 作者:
Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
Searching, Stepping, and Stomping: What Polymer Theory can teach us about the Molecular Motor Myosin V
- DOI:
10.1016/j.bpj.2012.11.3553 - 发表时间:
2013-01-29 - 期刊:
- 影响因子:
- 作者:
Michael Hinczewski;Riina Tehver;Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
Impact of TMAO on the preQ1 RNA Riboswitch Studied using Molecular Dynamics Simulations
- DOI:
10.1016/j.bpj.2011.11.1529 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Elizabeth Denning;Devarajan Thirumalai;Alexander D. MacKerell - 通讯作者:
Alexander D. MacKerell
Devarajan Thirumalai的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Devarajan Thirumalai', 18)}}的其他基金
Physical Models for Cancer Cells with Links to Alterations in Genome Organization
与基因组组织改变相关的癌细胞物理模型
- 批准号:
2310639 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Continuing Grant
Topics in Protein and RNA Folding and Dynamics
蛋白质和 RNA 折叠和动力学主题
- 批准号:
2320256 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
Topics in protein and RNA folding and dynamics
蛋白质和 RNA 折叠和动力学主题
- 批准号:
1900093 - 财政年份:2019
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
Physical Models for Cancer Progression
癌症进展的物理模型
- 批准号:
1708128 - 财政年份:2017
- 资助金额:
$ 100万 - 项目类别:
Continuing Grant
Topics in protein and RNA folding and dynamics
蛋白质和 RNA 折叠和动力学主题
- 批准号:
1636424 - 财政年份:2016
- 资助金额:
$ 100万 - 项目类别:
Continuing Grant
INSPIRE: Minimal adaptive and replicating cell
INSPIRE:最小适应性和复制细胞
- 批准号:
1523098 - 财政年份:2015
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
Topics in protein and RNA folding and dynamics
蛋白质和 RNA 折叠和动力学主题
- 批准号:
1361946 - 财政年份:2014
- 资助金额:
$ 100万 - 项目类别:
Continuing Grant
Workshop: International Meeting on Protein Folding and Dynamics; to be held October 15-17, 2012 in Bangalore, India
研讨会:蛋白质折叠和动力学国际会议;
- 批准号:
1241302 - 财政年份:2012
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
GRC: Protein Folding and Dynamics in Ventura, CA January 7-8, 2012
GRC:蛋白质折叠和动力学,加利福尼亚州文图拉,2012 年 1 月 7-8 日
- 批准号:
1157471 - 财政年份:2012
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
Creation of POLS-SAVI Node at the University of Maryland
在马里兰大学创建 POLS-SAVI 节点
- 批准号:
1206005 - 财政年份:2012
- 资助金额:
$ 100万 - 项目类别:
Continuing Grant
相似国自然基金
对有序实数域o-minimal扩展上可定义函数的研究
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Unique continuation and the regularity of elliptic PDEs and generalized minimal submanifolds
椭圆偏微分方程和广义最小子流形的唯一延拓和正则性
- 批准号:
2350351 - 财政年份:2024
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
Rotation 1: Mapping the evolutionary trajectories of newly evolved minimal proteins
第 1 轮:绘制新进化的最小蛋白质的进化轨迹
- 批准号:
2643473 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Studentship
C*-algebras Associated to Minimal and Hyperbolic Dynamical Systems
与最小和双曲动力系统相关的 C* 代数
- 批准号:
2247424 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Continuing Grant
Defining the Minimal Trigger for Human Centromere Formation
定义人类着丝粒形成的最小触发因素
- 批准号:
EP/X025675/1 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Fellowship
Dynamics and clinical significance of minimal residual disease in peripheral blood collected from high-risk neuroblastoma patients.
高危神经母细胞瘤患者外周血微小残留病的动态及临床意义。
- 批准号:
23K14977 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The road from vesicles to minimal cells: metabolism, reproduction, and evolution
从囊泡到最小细胞的道路:新陈代谢、繁殖和进化
- 批准号:
23K13070 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Severity analysis of minimal change nephrotic syndrome by multifaceted assessment of mitochondrial dysfunction
通过线粒体功能障碍的多方面评估来分析微小病变肾病综合征的严重程度
- 批准号:
23K15257 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
SBIR Phase I: An extravascular bipolar catheter for targeted nerve ablation with minimal collateral damage to surrounding tissues
SBIR 第一期:血管外双极导管,用于靶向神经消融,对周围组织的附带损伤最小
- 批准号:
2213155 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
A Variational Approach to Spectral Shift and Spectral Minimal Partitions
谱位移和谱最小划分的变分方法
- 批准号:
2247473 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Standard Grant
RUI: Implications of Non-Minimal Dark Sectors
RUI:非最小暗区的影响
- 批准号:
2310622 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Standard Grant