Theoretical Condensed Matter Physics

理论凝聚态物理

• 批准号: 0129848
• 负责人: Eric Siggia
• 金额: $ 45.3万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0129848&HistoricalAwards=false
• 关键词: Theoretical; Condensed; Matter; Physics

This grant is co-funded by the Divisions of Materials Research, Molecular and Cellular Biology, and Physics. The grant supports theoretical research in biological physics.Many problems in biology have a component that involves statistical mechanics either directly because the question is on the molecular scale, or indirectly because a probablistic model is being used to decode a genomic sequence.The internal Watson-Crick base pairing of RNA defines its secondary structure which is better delineated energetically than the corresponding elements in proteins. A kinetic Monte Carlo code has recently been written to follow the formation of secondary structure for RNA's up to ~ 400 bases in length and includes non-nested configurations (pseudoknots). The code will be applied to the ends of the molecule as in recent experiments.Protein trafficing in cells involves numerous steps where proteins are sorted and targeted, e.g., in the Golgi substrate as processed in successive cisternae by different enzymes. In collaboration with a laboratory at NIH, models which allow for Golgi enzyme localization in a connected membrane system will be devised and tested. These are alternatives to the prevailing ideas that either the substrate lives in fixed compartments and the enzymes flux through the compartments via an active process of sorting and vesicle transport, or the enzymes are fixed and the substrates are actively transported.There are now multiple fluorescent proteins that can be expressed in live cells (sometimes as chimeras with native proteins), which allow for measurement of their number in one cell as a function of time. In conjunction with an experimental group at Rockefeller, we are modeling the stochastic noise (due to a small number of molecules) in transcription and translation. More generally we will collaborate on experiments and theory to assess whether stochastic effects impact the fitness of bacteria.The regulation of gene transcription by short, e.g., 10-30 bp, motifs to which proteins bind and integrate environmental signals is important to many areas of biology. An algorithm has been devised which finds improbable strings of bases, based on the frequency of shorter strings present in an iteratively constructed 'dictionary.' It yielded many significant motifs when applied to yeast, and we intend to apply the algorithm to other organisms, as well as extend it to recognize fuzzy patterns. The comparison of related species is another way to recover regulatory motifs and we intend to apply a probablistic alignment code both to fit the evolution rate in noncoding sequence and assign probabilities to the regions which are more conserved than chance and thus functional. An algorithm to relate gene expression data directly to sequence and assign statistical significance has been tried on yeast and will be extended to other multicellualr organisms.%%%This grant is co-funded by the Divisions of Materials Research, Molecular and Cellular Biology, and Physics. The grant supports theoretical research in biological physics.Many problems in biology have a component that involves statistical mechanics either directly because the question is on the molecular scale, or indirectly because a probablistic model is being used to decode a genomic sequence. This research will investigate a variety of problems of current biological interest using techniques from theoretical condensed matter physics.***

该赠款由材料研究，分子和细胞生物学以及物理学的分裂共同资助。该赠款支持生物物理学的理论研究。生物学中的许多问题具有统计力学的成分，可以直接是因为该问题是在分子量表上或间接的，或者是因为概念性模型被用来解码基因组序列。RNA的内部watson-crick基础配对定义了其二级结构，其二级结构比与相应的元素更好地构成了相应的元素。 最近已经写了一个动力学蒙特卡洛密码，以遵循RNA的长度左右左右的二级结构的形成，并包括非巢式配置（Pseudoknots）。 该代码将与最近的实验一样应用于分子的末端。细胞中的蛋白质流量涉及许多步骤，其中蛋白质被分类和靶向，例如，在连续的硫斯基甲酸盐中通过不同酶处理的高尔基底物。 与NIH的实验室合作，将设计和测试在连接的膜系统中进行高尔基体定位的模型。 These are alternatives to the prevailing ideas that either the substrate lives in fixed compartments and the enzymes flux through the compartments via an active process of sorting and vesicle transport, or the enzymes are fixed and the substrates are actively transported.There are now multiple fluorescent proteins that can be expressed in live cells (sometimes as chimeras with native proteins), which allow for measurement of their number in one cell as a function of time. 与洛克菲勒（Rockefeller）的实验组结合使用，我们正在对转录和翻译中的随机噪声（由于少量分子）进行建模。 更普遍地，我们将在实验和理论上进行协作，以评估随机作用是否影响细菌的适应性。简短对基因转录的调节，例如10-30 bp，蛋白质结合和整合环境信号的基序对许多生物学领域都很重要。 已经设计了一种算法，该算法根据迭代构造的“词典”中存在的短字符串的频率，发现了不可能的碱基字符串。 当应用于酵母时，它产生了许多重要的基序，我们打算将算法应用于其他生物体，并将其扩展以识别模糊模式。 相关物种的比较是恢复调节基序的另一种方法，我们打算采用概率的比对代码以适合非编码序列的进化速率，又适合对比机会更保守的区域分配概率，从而比机会更具功能。 一种将基因表达数据直接与序列联系起来的算法和分配统计显着性已在酵母上进行了尝试，并将扩展到其他多ellicalualr生物体。%% %%此赠款是由材料研究，分子和细胞生物学和物理学的分裂共同资助的。该赠款支持生物物理学的理论研究。生物学中的许多问题具有涉及统计力学的成分，要么是因为问题是在分子量表上，要么是间接的，因为概念性模型被用于解释基因组序列。 这项研究将使用理论凝结物理学的技术调查当前生物学兴趣的各种问题。***