Dynamic Pattern in Chemically Reacting Systems

描述（由申请人提供）：我们对许多系统中参与信号转导和基因表达的分子成分了解很多，现在的重点转移到理解这些成分如何集成到网络中，以及这些网络如何转导它们接收的输入并在发育中的系统中产生所需的基因表达模式。发育是一个连续的过程，后期阶段建立在早期阶段的基础上，但在阶段内，信号和基因控制网络中往往存在多个反馈回路，这些反馈回路可以缓冲信号分子和其他成分波动引起的扰动。这项研究的长期目标之一是开发数学和计算工具，这些工具可用于阐明网络的结构特征，从而在面对参数、环境和分子波动时产生可靠的输出。黑腹果蝇是几个模型系统之一，其中许多涉及模式的信号转导和基因控制网络的组成部分是已知的。然而，对这些网络如何产生所需的基因表达的时空模式知之甚少。主要项目有：(1)果蝇的背-腹模式研究；(2)果蝇翅盘生长与模式研究；(3)非洲蛙爪蟾（Xenopus laevis）的背-腹模式研究。(1)的目的是进一步加深我们对随机波动和某些突变的作用的理解，并开始研究非受体（辅助）蛋白在调节信号传导中的作用。我们将为此开发一个通用模型，并分析胶原蛋白和表面结合蛋白等不同因素之间的平衡如何影响基因表达中的噪声和面对突变和其他扰动时的鲁棒性等特征。(2)的目的是开发和分析果蝇翅盘模式形成和生长的层次模型，以了解不同的信号通路如何在一个几何上真实的圆盘表示中相互作用。(3)的目的是了解爪蟾的BMP信号和模式，并确定爪蟾发育过程中大小适应的来源。

DESCRIPTION (provided by applicant): Much is known about the molecular components involved in signal transduction and gene expression in a number of systems, and the focus is now shifting to understanding how these components are integrated into networks, and how these networks transduce the inputs they receive and produce the desired pattern of gene expression in a developing system. Development is a sequential process in which later stages build on earlier stages, but within stages there are often multiple feedback loops in signaling and gene control networks that may serve to buffer against perturbations caused by fluctuations in signaling molecules and other components. One of the long range objectives of this research are to develop mathematical and computational tools that can be used to shed light on the structural characteristics of networks that lead to reliable outputs in the face of parametric, environmental and molecular fluctuations. Drosophila melanogaster is one of several model systems for which many of the components of the signal transduction and gene control networks involved in patterning are known. However, less is known about how these networks produce the desired spatio-temporal pattern of gene expression. The major projects are: (1) studies on dorsal-ventral patterning in Drosophila, (2) studies on growth and patterning in the wing disc of Drosophila, an (3) studies on dorsal-ventral patterning in the African frog Drosophila, Xenopus laevis. The aims under (1) are to further advance our understanding of the role of stochastic fluctuations and the role of certain mutants, and to begin a study of the role of non-receptor (auxiliary) proteins in modulating signaling. We will develop a general model for this and analyze how the balance between different factors such as collagen and surface bound proteins affect characteristics such as noise in gene expression and robustness in the face of mutations and other perturbations. The aims under (2) are to develop and analyze a hierarchy of models for pattern formation and growth in the Drosophila wing disc to understand how distinct signaling pathways interact in a geometrically- realistic representation of a disc. The objectives under (3) are to understand BMP signaling and patterning in Xenopus and to identify the source of size-adaptation in the development of Xenopus. PUBLIC HEALTH RELEVANCE: The research will advance our understanding of basic processes in developmental biology such as signal transduction, pattern formation and the control of organ size in developing systems. A better understanding of these fundamental processes will contribute to a better understanding of how systems respond to their environment, how normal development can be disrupted and perhaps abnormal development corrected. In particular, understanding growth control in normal systems will be essential for understanding aberrant control in cancer.