Collaborative Research: Dynamics of Boolean Networks and Gene Expression

本研究项目聚焦于复杂网络的一般属性，目的是阐明不同类型网络架构的功能含义。工作假设是，某些类别的布尔网络说明了构成生物有机体结构的组织原则。众所周知，这样的网络表现出截然不同的行为机制：有序的、混乱的和临界的。生物细胞属于这一类吗？现代基因阵列技术现在允许收集大量的基因表达数据，为这类问题提供了一个新的实验窗口。提出的研究旨在为设计此类实验和解释其结果建立一个有用的理论框架。该项目的具体目标包括确定无标度和模块化布尔网络中扰动后活动级联的标度定律，动态吸引子集的特征，以及与不同网络架构相关的它们之间的转换，以及当采用随机定时规则而不是传统的同步更新规则进行更新时对此类网络的分析。在所有情况下，注意力将集中在生物系统中可以测量的数量上，目前可用的实验数据将用于改进要研究的模型类别。该项目是高度跨学科的，需要动力系统理论和细胞与发育生物学专家之间的合作。该基金将用于为功能基因组学和生物信息学等新兴领域的本科生、研究生和博士后提供跨学科培训，在这些领域，传统上在物理背景下教授的分析技能以及细胞和分子生物学原理同样重要。

This research project focuses on the generic properties of complex networks, with the goal of elucidating the functional implications of different types of network architecture. The working hypothesis is that certain classes of Boolean networks illustrate principles of organization that underlie the structure of biological organisms. Such networks are known to exhibit fundamentally distinct regimes of behavior: ordered, chaotic, and critical. Do biological cells belong to one of these classes? Modern gene array techniques now permit the gathering of vast amounts of data on gene expression, providing a new experimental window on questions of this type. The proposed research aims to develop a useful theoretical framework for designing such experiments and interpreting their results. Specific aims of the project include the determination of scaling laws for cascades of activity following perturbations in scale-free and modular Boolean networks, the characterization of sets of dynamical attractors, and transitions between them, associated with different network architectures, and the analysis of such networks when stochastic timing rules are employed for updating rather than the traditional synchronous updating rules. In all cases, attention will be focused on quantities that can be measured in biological systems, and currently available experimental data will be used to refine the classes of models to be studied.The project is highly cross-disciplinary, requiring a collaboration between experts in dynamical systems theory and cell and developmental biology. Funds will be used to provide interdisciplinary training for an undergraduate student, a graduate student, and a postdoc in the burgeoning fields of functional genomics and bioinformatics, where analytical skills traditionally taught in physics contexts and principles of cell and molecular biology are equally important.