Dynamic Regulation of the Cell Cycle by the Proliferation Control (Rb) and Death Control (p53) Oncogenes

摘要奖：DMS-0342283首席研究员：Paul Brahnk这个项目旨在阐明哺乳动物细胞中与某些基因相关的控制机制的动力学原理和数学模型，以便将可用的实验信息组织到一个系统的、定量的框架中，并评估当前假说解释实验观察到的表型的能力。特别是，主要研究人员和合作者将通过RB-E2F研究细胞增殖控制，并通过P53-MDM2研究DNA修复和细胞死亡控制。这些生物模块的行为模型可以根据大量可用的实验数据进行测试，在这些模型中，可以测试和改进关于机制和路径的想法，也许可以探索在真实的分子生物学实验中难以测试的场景。在探索分子细胞生物学中的重要问题时，有用的数学方法包括动力学系统和分叉理论。动力系统是随着时间不断变化的自然现象的模型，而分叉理论研究的是在持续演化一段时间后可能在瞬间剧烈变化的现象的模型(想想气球在逐渐膨胀到过满状态后爆裂)。受特定基因调控的细胞过程既可以表现出稳定的行为，也可以表现出突然变化的行为，主要研究人员和合作者正在利用数学和计算工具研究重要的细胞周期(增殖、DNA修复和死亡控制)。这笔赠款是在DMS/NIGMS联合倡议下提供的，以支持数学生物学领域的研究资助。这是一项联合竞赛，由国家科学基金会的数学科学部和生物科学局和国立卫生研究院的国家普通医学研究所(NIGMS)主办，本奖项由NSF/BIO和NSF/DMS联合资助。

AbstractAward: DMS-0342283Principal Investigator: Paul BrazhnikThis project aims to elucidate dynamical principles and toformulate mathematical models of control mechanisms associatedwith certain genes in mammalian cells, in order to organizeavailable experimental information into a systematic,quantitative framework and to evaluate the ability of currenthypotheses to explain experimentally observed phenotypes. Inparticular, the principal investigator and collaborators willinvestigate cell proliferation control via Rb-E2F, and DNA repairand cell death control via p53-Mdm2. Models of the behavior ofthese biological modules can be tested against a substantialsupply of available experimental data, and within the models onecan test and refine ideas about mechanisms and pathways, perhapsexploring scenarios which are hard to test in real molecularbiology experiments.Mathematical methodologies useful in exploring important problemsin molecular cell biology include the theories of dynamicalsystems and bifurcation. Dynamical systems are models fornatural phenomena that change continuously with time, whilebifurcation theory studies models of phenomena that may changedramatically in an instant after evolving continuously for awhile (think of a balloon popping after it gradually inflates toan overfull state). Cellular processes regulated by particulargenes can exhibit both steady and suddenly changing behavior, andthe principal investigator and collaborators are studyingimportant cellular cycles (proliferation, plus DNA repair anddeath control) with mathematical and computational tools. Thisgrant is made under the Joint DMS/NIGMS Initiative to SupportResearch Grants in the Area of Mathematical Biology. This is ajoint competition sponsored by the Division of MathematicalSciences and the Directorate for Biological Sciences at theNational Science Foundation and the National Institute of GeneralMedical Sciences (NIGMS) at the National Institutes of Health,and the present award is funded jointly by NSF/BIO and NSF/DMS.