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

AbstractAward：DMS-0342283首席研究员：Paul Brazhnik该项目旨在阐明与哺乳动物细胞中某些基因相关的控制机制的动力学原理并制定数学模型，以便将可用的实验信息组织成系统的定量框架，并评估当前假设解释实验观察到的表型的能力。 特别是，主要研究者和合作者将通过Rb-E2 F研究细胞增殖控制，通过p53-Mdm 2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通过大量的实验数据进行测试，在这些模型中，人们可以测试和完善关于机制和途径的想法，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重要问题时有用的数学方法包括动力系统和分叉理论。 动力学系统是自然现象随时间不断变化的模型，而分叉理论研究的是现象在持续进化一段时间后可能在瞬间发生剧烈变化的模型（想想气球在逐渐膨胀到过满状态后爆裂）。 由特定基因调控的细胞过程可以表现出稳定和突然变化的行为，首席研究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，加上DNA修复和死亡控制）。 这项资助是根据DMS/NIGMS联合倡议，以支持数学生物学领域的研究赠款。 这是一个由数学科学部和国家科学基金会的生物科学理事会以及国立卫生研究院的国立普通医学科学研究所（NIGMS）赞助的联合竞赛，目前的奖项由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.