Theoretical Condensed Matter Physics

理论凝聚态物理

• 批准号: 0517138
• 负责人: Eric Siggia
• 金额: $ 43.5万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0517138&HistoricalAwards=false
• 关键词: Theoretical; Condensed; Matter; Physics

This grant is supported jointly by the Divisions of Materials Research and Molecular and Cellular Biosciences. All multi-celled organisms begin as an undifferentiated single celled egg and use the instructions written in the genome to create the specialized cells and organs of the adult. Recent genome sequencing projects reinforce earlier ideas that form is derived from how genes are regulated and coordinated; and by implication evolution, proceeds more by tinkering with the regulation of genes than creating new genes. The inference of gene regulation from the genome is still in its infancy, and many of the current genome sequencing projects are focused on clusters of related organisms with the intent of using interspecies comparisons as a filter for what is conserved and by implication most important for function. However, we are still largely ignorant of how regulatory information is encoded in the genome and simply comparing sequence may be like comparing the same sentence in two languages. Statistical mechanics is fundamentally concerned with computing the probabilities of patterns and assessing whether a sample is consistent with a model (more technically, the probability of the data giventhe model). The fruit fly has been a model for genetics and development for 100 years, and the genomes of 10 related species will be available in early 2005. Together with a developmental biology lab at Rockefeller University, we will ask whether our earlier successes in computing which regions of the genome control early embryonic patterning, can be made more quantitative by computing the partition function for binding the regulatory proteins to the DNA. The regulation we understand in fly will be mapped onto the other sequenced species, as well as the mosquito, as a test of our understanding and to see how regulation evolves.In a previous project we classified the basic molecular events through which regulatory sequence changes by studying recently diverged fly species. Since regulatory DNA directs gene expression by binding proteins, simulating how this property is preserved under mutation and selection should provide clues about how to decode natural sequence. The goal is to cast evolution as an optimization process and thus make it more a predictive theory, rather than a historical one.Cells have to coordinate many processes to divide and cells must cooperate to form an organism. The networks that accomplish this coordination are an important focus of current biology. The cell division cycle is arguable the basis of life itself, and many of the key genes are preserved between single celled yeast and mammals. Aberrations in the control of cell division and growth lead to cancer.The PI plans to process movies of single yeast cells growing into clusters with custom image processing software to investigate how cell to cell variability is indicative of the control network. Do larger cells divide more rapidly, and does the duration of the various phases of the cell cycle correlate? The cell cycle has to strictly order certain processes, e.g. DNA replication must precede the segregation of chromosomes, we will ask whether the fluctuations provide evidence for sub modules within the cell cycle (e.g. is DNA replication tied to bud emergence, and the expression of certain cyclin genes). A large collection of cell cycle mutants has been derived from screens on populations of cells and one should reexamine their properties at the single cell level. Specifically are certain genes responsible for maintaining the temporal coherence of submodules? As a representative cellular network, are there some aspects of the cell cycle that are better modeled as discrete, binary, systems rather than sets of differential equations?Broader Impacts: Enhance Infrastructure for Research and Education.The PI divides his time between The Rockefeller University, in New York City, and Cornell University, in Ithaca, NY, and collaborates with many individuals in the physical sciences and biology. He is on the thesis committee of many biology students, and the advisory panels for NIH funded centers in quantitative biology and foundations awarding grants for transitional research, where he is often the only quantitative member. This proposal will fund physical science students wanting to move into biology. We make our computational predictions available through customized web sites, and our software packages are distributed freely.

该赠款得到了材料研究以及分子和细胞生物科学的划分共同支持。 所有多细胞生物都以未分化的单细胞卵开始，并使用基因组中写的说明来创建成人的专业细胞和器官。最近的基因组测序项目加强了早期的观念，这些想法源自基因的调节和协调方式。并暗示进化，通过修补基因的调节而不是创建新基因而进行更多。 基因组的基因调节的推论仍处于起步阶段，许多当前的基因组测序项目集中在相关生物的簇上，目的是使用种间比较作为保守和对功能最重要的含义的过滤器。但是，我们仍然在很大程度上不知道如何在基因组中编码调节信息，并且简单地比较序列可能就像用两种语言比较同一句子。 统计力学在根本上与计算模式的概率有关，并评估样品是否与模型一致（从技术上讲，数据示为模型的概率）。果蝇已成为遗传学和发育的模型已有100年了，并且10种相关物种的基因组将于2005年初提供。与洛克菲勒大学的发展生物学实验室一起，我们将询问我们在计算基因组控制早期胚胎模式的哪些区域是否可以通过计算分区来构成型号来构成依据，以使构成型号的构成蛋白质，从而使构成构成蛋白质，从而使bection蛋白具有更大的定量。我们在苍蝇中理解的调节将映射到其他测序物种以及蚊子，以测试我们的理解并了解调节如何发展。在先前的项目中，我们对基本分子事件进行了分类，通过研究最近分散的蝇物种，调节序列通过这些事件进行了变化。由于调节性DNA通过结合蛋白来指导基因表达，因此模拟该特性如何在突变下保存和选择应提供有关如何解码自然序列的线索。目的是将进化作为优化过程，从而使其更具预测性理论，而不是历史理论。细胞必须协调许多过程以分裂，并且细胞必须合作形成生物体。 完成这种协调的网络是当前生物学的重要重点。细胞分裂周期是生命本身的基础，许多关键基因都保留在单细胞酵母和哺乳动物之间。控制细胞分裂和生长的畸变导致癌症。PI计划处理具有自定义图像处理软件的单酵母细胞的电影，以研究细胞变异性如何指示控制网络。较大的细胞会更快地分裂，并且细胞周期各个阶段的持续时间是否相关？ 细胞周期必须严格订购某些过程，例如DNA复制必须先于染色体的分离之前，我们将询问波动是否提供了细胞周期内亚模块的证据（例如，DNA复制与芽的出现相关，以及某些细胞周期蛋白基因的表达）。大量的细胞周期突变体是从细胞种群上的筛选中得出的，应该在单细胞水平上重新检查其特性。特别是某些基因是否负责维持子模型的时间连贯性？作为一个代表性的细胞网络，是否可以更好地建模细胞周期的某些方面，这些方面是离散的，二进制的，系统而不是一组微分方程？更广泛的影响：增强研究和教育的基础架构。PI在纽约市，纽约市和康奈尔大学（Ithaca）的洛克菲勒大学（Rockefeller University）之间的洛克菲勒大学（Rockefeller University）之间的时间分开，在Ithaca，与许多人一起进行了与许多人的合作和合作。 他是许多生物学学生的论文委员会，以及NIH资助的定量生物学和基金会的咨询小组，授予过渡性研究的赠款，他通常是唯一的定量成员。该建议将资助想要进入生物学的物理科学专业的学生。我们通过自定义网站提供计算预测，并且我们的软件包是自由分发的。