A Gene-Complete Computational Model of Yeast

描述 摘要 该提案的目标是建立一个计算模型，该模型可以模拟单个酵母细胞的完整生命周期，同时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”，并将彻底改变我们对生物学的看法，使我们能够研究以前从未研究过的主要细胞过程之间的相互作用。我们将证明这一点，结合计算建模和实验生物学，在一个详细的研究老化和寿命控制。要成功完成拟议的工作，必须解决几个智力挑战。例如，我们努力建立全细胞模型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，不同类型的生物过程，其中每一个可能是最好的描述使用不同的表示，将是至关重要的模型的集成方法。幸运的是私家侦探的专业知识是在模拟各种细胞过程，特别是在大规模集成不同的网络模型。我们所提出的工作不仅旨在通过构建全细胞计算机模型的“终极测试”，而且还旨在通过用户友好的网络界面使科学界和公众能够访问该模型。该项目的一个可交付成果将是一个基于网络的平台，该平台将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、代谢和细胞分裂。对于科学家来说，该平台将具有高级用户选项，以便其他研究人员可以将我们的方法适用于他们喜欢的任何细胞类型。我们预计，这可能会导致一个广泛的实施研究，使用计算建模和模拟，以指导实验计划和生物发现。 公共卫生相关性 本研究的总体目标是

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