BIOCOMPLEXITY--Multiscale Simulation of Avian Limb Development

0083653 Glazier发育中的多细胞生物体在形状和形式上表现出巨大的变化，以及特化（分化）细胞类型（例如神经元和肌肉纤维）的快速变化的空间组织的出现。这些事件，产生身体计划和各种器官，依赖于调控基因表达，细胞之间的相互作用，以及协调的细胞运动。基因表达本身并不能完全解释身体结构、特定形式和形状的出现。在发育过程中，遗传学和生物化学与单个细胞和细胞聚集体的物理特性相互作用，使其成为一个极其复杂的多尺度过程。然而，正如在许多复杂的过程中一样，如果使用适当的技术来分析发育中的生物体，人们可以在各个层次上发现动态和组织规则。这个项目汇集了生物学家、实验和理论物理学家、数学家和计算机科学家，他们每个人都有分析个体生物物理问题的经验，并将他们的专业知识用于特定的发育过程-脊椎动物肢体的形成。实验和理论方法将用于研究肢体芽从体壁中出现，调节细胞聚集的基因的控制，肢体骨骼模式的时空调节，以及神经纤维从脊髓长入肢体。这项工作将导致多层次的表征，包括亚细胞，细胞和超细胞机制，这将提供脊椎动物肢体发育的因果关系的理解，以及产生分析工具，可用于研究发育生物学中的类似问题。这些工具将包括用于解决不可避免的复杂数学方程系统的软件，这些方程描述了活胚胎中发现的遗传和物质特性的相互作用。新的软件将被建立和分发，不仅用于模拟肢体发育，还用于模拟其他类型的器官形成和疾病（例如肿瘤转移和血管形成）。总体战略代表了朝着真正的动物发育综合研究迈出的一步，以兑现过去十年基因测序项目的承诺。

0083653GlazierDeveloping multicellular organisms exhibit dramatic changes in shape and form, as well as the emergence of rapidly changing spatial organization of specialized (differentiated) cell types, e.g. neurons and muscle fibers. These events, which generate the body plan and the various organs, depend on regulated gene expression, elaborate interactions between and among cells, and coordinated cell movement. Gene expression by itself cannot give a full account of the emergence of body plans, specific forms and shapes. Genetics and biochemistry interact with the physical properties of individual cells and cell aggregates in the course of development, making it a multiscale process of enormous complexity. As in many complex processes, however, one can discover dynamical and organizational rules at various levels if appropriate techniques are used to analyze developing organisms. This project brings together biologists, experimental and theoretical physicists, mathematicians, and computer scientists, each of whom has experience analyzing individual biophysical problems, and brings their expertise to bear on a specific developmental process-the formation of the vertebrate limb. Experimental and theoretical methods will be used to investigate the emergence of the limb bud from the body wall, the control of genes mediating cell aggregation, the spatiotemporal regulation of the limb skeletal pattern, and the ingrowth of nerve fibers into the limb from the spinal cord.This work will result in a multilevel characterization including subcellular, cellular and supracellular mechanisms which will provide a causal understanding of vertebrate limb development, as well as generate analytical tools that can be used to study similar problems in developmental biology. These tools will include software for solving the inevitably complex systems of mathematical equations that describe the interplay of genetic and material properties found in living embryos. New software will be built and distributed to model not only limb development, but also other types of organ formation and illness (e.g. tumor metastasis and vascularization). The overall strategy represents a step towards genuinely integrated research on animal development to deliver on the promise of the gene sequencing projects of the previous decade.