A Gene-Complete Computational Model of Yeast

描述 摘要 这项建议的目标是建立一个计算模型，可以模拟单个酵母细胞的完整生命周期，考虑到所有注释的基因。这被称为“理解简单细胞的终极测试”，它将使我们能够检查以前从未研究过的主要细胞过程之间的相互作用，从而彻底改变我们看待生物学的方式。我们将结合计算建模和实验生物学，在对衰老和寿命控制的详细研究中证明这一点。要成功完成拟议的工作，必须解决几个智力挑战。例如，我们建立全细胞模型的努力的一个主要组成部分将取决于新的建模方法的发展，适用于大规模。此外，集成不同类型生物过程的模型的方法将是至关重要的，每一种生物过程都可以使用不同的表示法进行最佳描述。幸运的是，P.I.的特殊专长是对各种细胞过程进行建模，特别是在大规模整合不同的网络模型。我们拟议的工作不仅旨在通过建立全细胞计算机模型的“终极测试”，而且通过一个用户友好的网络界面使科学界和普通公众能够访问它。该项目的一个成果将是一个基于网络的平台，允许用户跟踪和干扰生物过程，如DNA复制、RNA转录和调节、蛋白质合成、新陈代谢和细胞分裂。对于科学家来说，该平台将拥有高级用户选项，这样其他研究人员就可以根据他们喜欢的细胞类型(S)来调整我们的方法。我们预计，这可能会导致研究的广泛实施，即使用计算建模和模拟来指导实验计划和生物发现。 公共卫生相关性 这项研究的总体目标是

DESCRIPTION Abstract The target of this proposal is to build a computational model that can simulate a complete life cycle of a single yeast cell, taking into account all of the annotated genes. This has been called "the ultimate test of understanding a simple cell" and will revolutionize how we view biology, by allowing us to examine interactions between major cellular processes which have never been studied before. We will demonstrate this point, integrating computational modeling and experimental biology, in a detailed study of aging and lifespan control. Several intellectual challenges will have to be addressed to complete the proposed work successfully. For example, a major component of our effort to build a whole-cell model will depend on the development of new modeling approaches, applicable at a large scale. Additionally, methods for the integration of models for different types of biological processes, each of which may be best described using different representation, will be critical. Fortunately, the particular expertise of the P.I. is in modeling a variety of cellular processes, and in particular integrating different network models at the large scale. Our proposed work aims not only to pass the "ultimate test" of building a whole-cell computer model, but to make it accessible to the scientific community and the general public through a user-friendly web interface. One deliverable of the project will be a web-based platform which will allow the user to track and perturb biological processes such as DNA replication, RNA transcription and regulation, protein synthesis, metabolism and cell division. For scientists, the platform will have advanced user options, so that other researchers can adapt our methods to whichever cell type(s) they prefer. We anticipate that this could lead to a broad implementation of research which uses computational modeling and simulation to guide experimental programs and biological discovery. Public Health Relevance The broad goal of this res