Temporal and spatial effects on expression and function

对表达和功能的时间和空间影响

• 批准号: 7418353
• 负责人: AIMEE M DUDLEY
• 金额: $ 27万
• 依托单位: INSTITUTE FOR SYSTEMS BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7418353
• 关键词: Animal Model; Area; Award; Bacteria; Biochemical Pathway; Biological; Biological Process; Cataloging; Catalogs; Cell Cycle; Cell Cycle Stage; Cell Extracts; Cell physiology; Cells; Church; Computer Analysis; Computer Simulation; Condition; Data; Data Analyses; Data Set; Development; Ensure; Environment; Evolution; Faculty; Frequencies; Fungal Genome; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genome; Genomics; Glass; Glucose; Goals; Growth; Iron; Label; Laboratories; Laboratory Research; Localized; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolism; Methodology; Mitochondria; Modeling; Modification; Mutation; Mycoplasma pneumoniae; Numbers; Oligonucleotides; Open Reading Frames; Organelles; Pathway interactions; Phase; Phase Transition; Phenotype; Phylogenetic Analysis; Pneumonia; Post-Translational Protein Processing; Process; Protein Analysis; Proteins; Proteome; Proteomics; RNA; Reagent; Regulation; Research; Research Design; Saccharomyces cerevisiae; Sampling; Score; Spottings; System; Techniques; Technology; Time; Transcript; Translations; Work; Yeast Model System; Yeasts; base; career; cell growth; computerized tools; cost; experience; functional genomics; genetic linkage; genome-wide analysis; human disease; improved; interest; mathematical model; multidisciplinary; mutant; network models; numb protein; programs; promoter; research study; skills; transcription factor

DESCRIPTION (provided by applicant): Despite their importance in nearly all biological processes, the impacts of spatial and temporal effects on gene expression, protein abundance, and protein modification are greatly underrepresented in genome-wide analyses. This proposal is aimed at the development and implementation of new experimental and computational tools capable of measuring and modeling spatial and temporal biological data, focusing on the poorly studied relationship between the cell cycle and mitochondrial function in the model organism, S.cerevisiae. The research plan focuses on experimental systems for the large-scale measurement of mutant phenotype and genetic linkage, whole-genome RNA expression analysis using a system of RNA abundance, quantitation on an absolute scale, and mass spectrometry-based identification of proteins and protein modification states present in subcellular organelles. The computational analysis of this data will include the transcriptional regulatory network under these conditions, a model of yeast metabolism, and the relationship between evolution and organelle function. All of the techniques and methodologies developed in this study are designed to be genome-wide, high-throughput, cost-effective, and readily transferable to other systems. In addition to developing much needed technologies and computational tools, this project will also contribute important biological results that will further our understanding of previously characterized genes and pathways that are likely to be relevant to human disease. The candidate's long-term career goal is the establishment of an academic research laboratory focusing on the analysis of biological problems using a combination of functional genomics and computational modeling of biological processes. The Genome Scholar phase of the award will be used to improve computational skills and to acquire experience in the use of protein mass spectrometry. The Faculty Transition phase of the award will be used to establish a multidisciplinary environment for the conduct of genomics research.

描述（由申请人提供）：尽管空间和时间效应对基因表达、蛋白质丰度和蛋白质修饰的影响在几乎所有生物过程中都很重要，但在全基因组分析中却大大低估了它们。该提案旨在开发和实施能够测量和建模空间和时间生物数据的新实验和计算工具，重点关注模型生物酿酒酵母中细胞周期和线粒体功能之间的关系。该研究计划的重点是大规模测量突变表型和遗传连锁的实验系统、使用RNA丰度系统进行全基因组RNA表达分析、绝对规模定量以及基于质谱的蛋白质和蛋白质修饰鉴定存在于亚细胞器中的状态。这些数据的计算分析将包括这些条件下的转录调控网络、酵母代谢模型以及进化与细胞器功能之间的关系。本研究中开发的所有技术和方法均设计为全基因组、高通量、经济高效且易于转移到其他系统。 除了开发急需的技术和计算工具外，该项目还将贡献重要的生物学结果，这将进一步加深我们对先前表征的可能与人类疾病相关的基因和途径的理解。 候选人的长期职业目标是建立一个学术研究实验室，专注于结合功能基因组学和生物过程计算建模来分析生物问题。该奖项的基因组学者阶段将用于提高计算技能并获得使用蛋白质质谱法的经验。该奖项的教师过渡阶段将用于建立进行基因组学研究的多学科环境。