Mathematical Sciences: Chromosome Geometry and Chromosome Aberrations

数学科学：染色体几何和染色体畸变

• 批准号: 9532055
• 负责人: Rainer Sachs
• 金额: $ 15万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-15 至 2000-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9532055&HistoricalAwards=false
• 关键词: Mathematical; Sciences; Chromosome; Geometry; Aberrations

Sachs 9532055 The investigator models chromosome aberrations in live mammalian cells, emphasizing implications for large-scale chromosome geometry and for the biology of ionizing radiation damage. He analyzes formation of chromosome aberrations after induction of DNA double strand breaks by radiation during the interphase part of the cell cycle, using probabilistic models for DNA geometry, motion, and reactions at the macromolecular level. For example, one area concerns the combinatorics and kinetics of illegitimate recombinations, involving the exchange of fragments between several different chromosomes. Polymer models are used for large-scale chromosome structure and motion. Statistical questions arise when very detailed experimental information about specific individual chromosomes is made available by modern fluorescent in situ hybridization techniques; these he addresses by extending already developed Monte-Carlo simulations. The study involves developing computer algorithms, explicitly solving stochastic process models, and collaborating with experimental groups. Ionizing radiation damage to chromosomes is being studied mathematically. When ionizing radiation hits cells, as occurs for example in tumor radiotherapy or radiation accidents, one gets breakage and large-scale reshuffling of DNA molecules. The resulting chromosome aberrations have been implicated as symptoms or causes of most major radiobiological effects. They are especially important in biodosimetry, the estimation of past exposure to radiation dose by looking at residual cellular damage. They are also a window on fundamental biology because they are influenced by, and symptomatic of, chromosome geometry and motion. Recent developments, whereby specific human chromosomes can be "painted" different colors, have dramatically increased the amount of information obtained from aberration studies. A very rich and colorful variety of aberrations can now be observed. Trying to und erstand the number and kind of reshufflings one sees leads to mathematically nontrivial problems, amenable to computer simulations or "pen and paper" calculations. The simulations and calculations are being carried out under the grant. The results allow systematic comparisons of cellular radiation damage effects observed by different laboratories using different chromosome painting schemes. In addition, mechanistic modeling of how chromosome aberrations evolve in time is helping to attack the main mystery of radiobiology: how to extrapolate from the larger doses needed for statistically significant experimental results to the much smaller doses relevant to risk estimates for large human populations subjected to radiation from environmental or man-made sources.

萨克斯9532055 研究者在活的哺乳动物细胞中模拟染色体畸变，强调大规模染色体几何学和电离辐射损伤生物学的影响。 他分析了在细胞周期的间期部分通过辐射诱导DNA双链断裂后染色体畸变的形成，使用DNA几何形状，运动和大分子水平反应的概率模型。 例如，一个领域涉及非法重组的组合学和动力学，涉及几个不同染色体之间的片段交换。 聚合物模型用于大规模染色体结构和运动。 统计问题出现时，非常详细的实验信息，具体的个别染色体是由现代荧光原位杂交技术，这些他地址通过扩展已经开发的蒙特-卡罗模拟。 这项研究涉及开发计算机算法，明确解决随机过程模型，并与实验组合作。 电离辐射对染色体的损伤正在进行数学研究。 当电离辐射击中细胞时，例如在肿瘤放射治疗或辐射事故中发生的，人们会得到DNA分子的断裂和大规模重组。 由此产生的染色体畸变被认为是大多数主要放射生物学效应的症状或原因。 它们在生物剂量测定中特别重要，生物剂量测定是通过观察残留的细胞损伤来估计过去受到的辐射剂量。 它们也是基础生物学的一个窗口，因为它们受到染色体几何形状和运动的影响，并表现为染色体几何形状和运动的症状。 最近的发展，即特定的人类染色体可以被“涂”上不同的颜色，大大增加了从畸变研究中获得的信息量。 现在可以观察到非常丰富多彩的各种像差。 试图理解人们看到的重组的数量和种类会导致数学上的非平凡问题，这些问题可以通过计算机模拟或“纸笔”计算来解决。 目前正在赠款下进行模拟和计算。 这些结果允许系统比较不同实验室使用不同染色体涂绘方案观察到的细胞辐射损伤效应。 此外，染色体畸变如何随时间演变的机械模型有助于解决放射生物学的主要谜团：如何从统计学显著实验结果所需的较大剂量外推到与遭受环境或人为来源辐射的大量人群的风险估计相关的小得多的剂量。