Investigations on the integrated behavior of molecular r

分子r整合行为的研究

• 批准号: 7337939
• 负责人: KURT KOHN
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7337939
• 关键词: Investigations; integrated; behavior; molecular

An enormous amount of information has accumulated about the molecular components that govern the cell division cycle and apoptosis; information that is crucial to the development of new anti-cancer therapies. However, the relevant molecular interaction networks are so complicated that it is often difficult to understand exactly how they function. Diagramming these networks presents a major challenge, because of the large role played by multimolecular complexes and modification contingencies . Yet comprehensive diagrams, using a standardized notation, are essential in the same way that circuit diagrams are essential in electronics. Several years ago, we devised a notation for molecular interaction maps (MIM) that many in the field now consider to be the best way to represent the networks in detail. We have used MIMs in many publications and examples have been prominently displayed in journal issues (such as being featured on the cover). MIMs however have not yet been widely used by others, presumably because of the effort required to learn the rules of the notation. Our colleagues have found the effort to be well worth while, in part because adhering to the rules of the MIM notation imposes a discipline of logic that enforces clear understanding. In order to help others adopt the notation, we published an article this year that more clearly defines the rules of the notation and that provides a systematic set of examples (Kohn et al. (2006) Mol. Biol. Cell 17: 1-13). The article can serve both as a reference manual and as a tutorial. By publishing this article in a major cell biology journal, we aimed for the broad cell biology community, rather than narrowly for bioinformaticists and systems biologists. The editors selected examples of our molecular interaction maps for display on the journal cover in order to bring our method to the attention of a wide audience of cell biologists.Relevant to bioinformatics and systems biology, we prepared another article (Kohn et al. (2006) Mol. Syst. Biol., in press), in which we address two major issues. First, we show the advantages of the MIM notation relative to other proposed notations. Second, we show how the MIM notation can represent networks for combinatorial simulation, a capability not shared by any other proposed notation. To demonstrate this point, we prepared a concise representation of a combinatorial simulation of the core of epidermal growth factor signaling recently published by Blinov et al, consisting of over 3000 individual reactions. This insight then led to a collaboration with Michael Blinov et al, in which we plan to mesh our MIM notation with their combinatorial network program. On the computation front this year, our group began a simulation study of the role of Mdmx in the response of p53 to DNA damage. In collaboration with Dr. Mirit Aladjem in our Laboratory, we plan to link simulation results with experiments.

关于控制细胞分裂周期和细胞凋亡的分子组分，已经积累了大量的信息;这些信息对于开发新的抗癌疗法至关重要。然而，相关的分子相互作用网络是如此复杂，以至于通常很难准确理解它们是如何发挥作用的。绘制这些网络图是一个重大挑战，因为多分子复合物和修饰偶然性发挥了很大的作用。然而，使用标准符号的综合图是必不可少的，就像电路图在电子学中是必不可少的一样。几年前，我们设计了一种分子相互作用图（MIM）的符号，该领域的许多人现在认为这是详细表示网络的最佳方式。我们在许多出版物中使用了MIM，并且在期刊中突出显示了示例（例如在封面上）。然而，MIM还没有被其他人广泛使用，大概是因为需要努力学习符号规则。我们的同事们发现，这种努力是值得的，部分原因是遵守MIM符号的规则强加了一种逻辑纪律，这种纪律强制了清晰的理解。为了帮助其他人采用该符号，我们今年发表了一篇文章，更清楚地定义了该符号的规则，并提供了一组系统的示例（Kohn et al.（2006）Mol. Cell 17：1-13）。这篇文章既可以作为参考手册，也可以作为教程。通过在主要的细胞生物学杂志上发表这篇文章，我们的目标是广泛的细胞生物学社区，而不是狭隘的生物信息学家和系统生物学家。编辑们选择了我们的分子相互作用图的例子用于在杂志封面上展示，以便使我们的方法引起广大细胞生物学家的注意。系统生物学，在这篇文章中，我们讨论了两个主要问题。首先，我们展示了MIM符号相对于其他符号的优势。其次，我们展示了如何MIM符号可以表示网络的组合仿真，没有共享的任何其他建议的符号的能力。为了证明这一点，我们准备了一个简明的组合模拟的核心表皮生长因子信号最近公布的Blinov等人，包括超过3000个单独的反应。这一见解随后导致了与Michael Blinov等人的合作，我们计划将我们的MIM符号与他们的组合网络程序相结合。在今年的计算方面，我们的团队开始模拟研究Mdmx在p53对DNA损伤的反应中的作用。在我们实验室的Mirit Aladjem博士的合作下，我们计划将模拟结果与实验联系起来。