Human Quantitative Dynamics

 描述(申请人提供)：随着我们利用过去15年中获得的大量基因组和表观基因组学知识来了解健康和疾病，人们越来越意识到，我们需要对各种细胞类型和组织的组成成分的浓度和相互作用进行量化了解。这些知识对于建立预测的动力学模型将基因组和表观基因组特征与生化和生理功能联系起来是必要的。为了获得这一知识，有必要通过实验确定和确定所有蛋白质(和其他细胞成分)的浓度，以及支配它们在人体主要器官的所有细胞类型中相互作用的动力学参数。这种对蛋白质及其相互作用的定量和动态实验编目将一端植根于人类基因组和转录组，另一端植根于人类细胞的生理反应。当量化数据被组织到数据库中时，将是最有用的，该数据库能够建立动态ODE和PDE模型以及网络模型。为了确保这些动力学参数的重复性和广泛使用，描述实验的元数据应该既深入又广泛。为了为人类定量动力学(HQD)项目制定一个自下而上的社区驱动计划，我们正在为一个研讨会寻求部分支持，该研讨会将来自不同社区的研究人员聚集在一起，他们通常不会彼此见面。这将包括分子神经生物学家、细胞免疫学家、胃肠生物学家、化学和机械工程师、生物信息学研究人员和动力学建模人员。研讨会将在贝塞斯达的国家卫生研究院举行，并将免费开放。在这次研讨会上，这些研究人员将分析最近完成的大型项目的优势、劣势和成本/效益比；评估当前的知识水平，确定试点项目计划的轮廓，以及未来研讨会的轮廓，这些研讨会可以制定和评估更深入的计划，即我们如何聚集在一起，开发资源和技术，以实现对人类细胞生物学和生理学的定量和预测性了解。

 DESCRIPTION (provided by applicant): As we use the vast genomic and epigenomic knowledge obtained over the past fifteen years to understand health and disease, there is a growing realization that we need to develop a quantitative understanding of the components of various cell types and tissues in terms of their concentrations and interactions. This knowledge is necessary to build predictive dynamical models to connect the genomic and epigenomic characteristics to biochemical and physiological functions. To obtain this knowledge it will be necessary to experimentally identify and determine concentrations all proteins (and other cellular components) along with the kinetic parameters that govern their interactions in all cell types from major organs of the human body. This quantitative and dynamic experimental cataloging of proteins and their interactions will be anchored in the human genome and transcriptome at one end, and human cell physiological responses at the other. The quantitative data will be most useful when organized in a database that enable building of dynamical ODE and PDE models as well as network models. To ensure reproducibility and wide usage of these kinetic parameters the metadata describing experiments should be both deep and broad. To develop a bottom-up community driven plan for a Human Quantitative Dynamics (HQD) Project we are seeking partial support for a workshop for which bring together researchers from different communities who would generally not meet with one another. This would include molecular neurobiologists, cellular immunologists, gastrointestinal biologists, chemical and mechanical engineers, bioinformatics researchers and dynamical modelers. The workshop will be held at the NIH in Bethesda and will be open and free. At this workshop these researchers will analyze the strengths, weaknesses and cost /benefit ratios of recently completed large scale projects; evaluate the current level of knowledge, identify the contours of a plan for a pilot project and for future workshops that can develop and assess more in-depth plans of how we can come together to develop resources and technologies that can enable quantitative and predictive understanding of human cell biology and physiology.