THEORETICAL ANALYSIS OF FUNCTIONAL MODULES

这项提议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中的参数的模块，以及提供生物过程模拟控制的模块。通过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。那些共享的原则将是该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，研究都将使用迭代循环的数值和分析方法 这两种方法之间的差异使人们逐渐更广泛地理解不同模块所体现的原则。1)布尔模块：主题模块控制果蝇的发育(分割和背腹模式)，或者是将在项目5中研究的合成模块。在所有情况下，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允许模块执行其正常功能、失败或执行新的、可能对进化有用的功能。2)测量模块：主题模块检测细菌和酵母中的浓度梯度(项目3)。它们分别监测时间和空间的变化，彼此独立地进化，对它们的理解也截然不同。对两者的研究将比较理论在理解的早期和后期阶段的作用，并寻找必须反映进化约束操作的共同原则。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。理论和实验将结合起来，区分本质上不同的模型，然后提炼出正确的模型。

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.