Dynamic Pattern in Chemically Reacting Systems

描述(申请人提供)：许多系统中涉及信号转导和基因表达的分子组件已知很多，现在的重点转移到了解这些组件如何整合到网络中，以及这些网络如何转导它们接收的输入并在发展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，在这个过程中，后期建立在早期阶段的基础上，但在各个阶段中，信号和基因控制网络中往往有多个反馈环路，这些环路可能用于缓冲信号分子和其他组件的波动造成的干扰。这项研究的长期目标之一是开发可用于阐明网络的结构特征的数学和计算工具，这些结构特征导致在面对参数、环境和分子波动时产生可靠的输出。果蝇黑腹果蝇是已知参与构图的信号转导和基因控制网络的许多组件的几个模型系统之一。然而，人们对这些网络如何产生所需的基因表达时空模式知之甚少。主要项目有：(1)果蝇背腹纹的研究，(2)果蝇翼盘生长和纹饰的研究，(3)非洲蛙背腹纹的研究。(1)的目的是进一步加深我们对随机波动的作用和某些突变体的作用的理解，并开始研究非受体(辅助)蛋白在调节信号中的作用。我们将为此开发一个通用模型，并分析不同因素(如胶原和表面结合蛋白)之间的平衡如何影响特征，如基因表达中的噪声和面对突变和其他扰动时的稳健性。(2)项下的目的是开发和分析果蝇翼盘中图案形成和生长的模型的层次结构，以了解不同的信号通路如何在几何逼真的盘表示中相互作用。(3)项下的目标是了解非洲爪哇的BMP信号和模式，并确定非洲爪哇发育过程中大小适应的来源。 公共卫生相关性：这项研究将促进我们对发育生物学的基本过程的理解，如信号转导、模式形成和发育系统中器官大小的控制。更好地理解这些基本过程将有助于更好地理解系统如何对其环境作出反应，如何扰乱正常的发展，以及可能纠正不正常的发展。特别是，了解正常系统中的生长控制对于了解癌症中的异常控制将是至关重要的。

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.