THEORETICAL ANALYSIS OF FUNCTIONAL MODULES

功能模块理论分析

• 批准号: 7557324
• 负责人: DANIEL SEBASTIAN FISHER
• 金额: $ 5.22万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7557324
• 关键词: Bacteria; Behavior; Binding; Biochemical Reaction; Biological; Biological Process; Case Study; Cells; Chemotaxis; Class; Collaborations; Condition; Detection; Development; Drosophila genus; Embryo; Environment; Equation; Escherichia coli; Eukaryota; Eukaryotic Cell; Event; Goals; Growth; Intuition; Length; Measurement; Measures; Methods; Mitotic spindle; Modeling; Modification; Molecular; Monitor; Motion; Operative Surgical Procedures; Output; Pattern; Performance; Pheromone; Process; Property; Range; Regulation; Role; Sorting - Cell Movement; Staging; Structure; System; Time; Variant; Work; Xenopus; Yeasts; analog; analytical tool; circadian pacemaker; desire; digital; egg; insight; interest; novel; receptor; research study; response; theories; tool

This proposal will establish a productive dialogue between experiment and theory, create models that predict the behavior of biological systems, and develop tools that explain how such models work. The studied modules are of three classes: those that perform Boolean functions, those that quantitatively measure parameters in the internal or external environment, and those that give analog control of biological processes. Modeling these different sorts of module permits comparisons of the principles that lie behind their function. Those that are shared will be candidates for general, explanatory principles that the group is especially interested in finding. In all cases, studies will use both numerical and analytic methods with iterative cycles between the two approaches leading to progressively broader understanding of the principles that the different modules embody. 1) Boolean modules: The subject modules control Drosophila development (segmentation and dorso-ventral patterning) or are synthetic modules that will be studied in Project 5. In all cases, the goal is to find and then generalize analytical tools that can predict whether a particular set of variables will allow the module to perform its normal function, fail, or perform a novel, and perhaps evolutionarily useful, function. 2) Measurement modules: The subject modules detect concentrations gradients in bacteria and yeast (Project 3). They monitor temporal and spatial changes, respectively, have evolved independently of each other, and are understood to very different extents. Studying both will compare the role of theory at early and late stages of understanding, and search for common principles that must reflect the operation of evolutionary constraints. 3) Analog modules: The subject module is responsible for assembling a mitotic spindle of a predetermined length. Theory and experiment will combine to discriminate between qualitatively different models and then refine the correct one.

该提案将在实验和理论之间建立富有成效的对话，创建预测生物系统行为的模型，并开发解释这些模型如何工作的工具。所研究的模块分为三类：执行布尔函数的模块，定量测量内部或外部环境参数的模块，以及模拟生物过程控制的模块。对这些不同类型的模块进行建模可以比较其功能背后的原理。那些共享的将是小组特别感兴趣的一般性解释性原则的候选者。在所有情况下，研究将使用数值和分析方法与迭代周期 这两种方法之间的差异导致对不同模块所体现的原则的逐步更广泛的理解。1)布尔模块：主题模块控制果蝇的发展（分割和背腹图案）或合成模块，将在项目5中进行研究。在所有情况下，我们的目标都是找到并推广分析工具，这些工具可以预测一组特定的变量是否会允许模块执行其正常功能，失败，或者执行一个新的，也许在进化上有用的功能。2)测量模块：主题模块检测细菌和酵母菌的浓度梯度（项目3）。它们分别监测时间和空间的变化，相互独立地演变，理解的程度也大不相同。研究两者将比较理论在理解早期和晚期阶段的作用，并寻找必须反映进化约束运作的共同原则。3)模拟模块：主题模块负责组装预定长度的有丝分裂纺锤体。理论和实验将联合收割机相结合，以区别不同的模型，然后完善正确的。