Real Time Functional Genomics of Metabolism/Cell Arrays

代谢/细胞阵列的实时功能基因组学

• 批准号: 6467909
• 负责人: Martin L Yarmush
• 金额: $ 29.41万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6467909
• 关键词: biochemistry; bioengineering /biomedical engineering; biological signal transduction; biomedical automation; biomedical equipment development; cell biology; cell population study; chemical structure function; computer data analysis; computer program /software; computer system design /evaluation; environmental stressor; fluid flow; fluorescence spectrometry; functional /structural genomics; gene environment interaction; gene expression; green fluorescent proteins; informatics; liver cells; metabolism; microarray technology; protein engineering; proteomics; recombinant proteins; time resolved data

DESCRIPTION (provided by applicant): The tools of modern biology are revolutionizing biomedical research, enabling an exponential growth in the acquisition of data regarding genes, proteins, and their structures and functions in normal and diseased states. Among these advances, the ability to monitor profiles of genes, and to a lesser extent, protein expression accurately, and on a large scale are notable. However, it is often not easy to correlate the trends and relationships observed in normal or abnormal states to the phenotype resulting from the gene expression profile. For physiological states involving metabolic derangements, gene expression profiling does not fully explain the complex molecular mechanisms involved. Thus, in order to develop a comprehensive understanding of metabolic states, it is essential to understand both the gene expression events as well as the cytoplasmic events that control changes in metabolites. The proposed research seeks to accomplish the following: (1) To determine the genes whose expression is altered by molecular mediators of the stress response and to generate green fluorescence protein (GFP)-tagged expression constructs of these genes; (2) To use microfabricated and microfluidic techniques for developing a living cell array systems where differentiated cells can be cultivated and exposed to multiple inputs; (3) To obtain temporal gene expression profiles using the living cell array that has been exposed to combinatorial mixtures of stress mediators that closely mimics the physiological stress response and to use this information to predict the molecular events that determine the cell's progression to recovery or failure during stress. This proposal is an interdisciplinary project that integrates scientific inputs from biology, engineering, and computational methods. Each element of the proposal is integral to the success of the overall project and we anticipate that this will provide excellent training to the postdoctoral fellow and graduate students working on this project. The results should provide valuable new information on the molecular mechanisms governing metabolic states, which will be disseminated via peer-reviewed publications and presentations at national conferences. In summary, the proposed work seeks to provide fundamental research and a base of personnel equipped to solve problems in fields such as metabolic engineering where complex biological phenomena are under investigation.

描述（由申请人提供）：现代生物学的工具正在彻底改变生物医学研究，从而实现了指数增长 获取有关基因，蛋白质及其结构的数据以及 在正常状态和患病状态下起作用。在这些进步中， 监测基因的曲线，并在较小程度上蛋白质表达 准确地说，很大程度上是值得注意的。但是，通常并不容易 将在正常状态或异常状态下观察到的趋势和关系与 基因表达谱产生的表型。用于生理 涉及代谢危险的状态，基因表达分析不可能 充分解释涉及的复杂分子机制。因此，为了 对代谢状态有全面的了解，必须 了解基因表达事件以及细胞质事件 控制代谢物的变化。拟议的研究试图完成 以下内容：（1）确定表达被改变的基因 应力反应的分子介质并产生绿色荧光 这些基因的蛋白质（GFP）标记的表达构建体； （2）使用 用于开发活细胞阵列的微生物和微流体技术 可以种植分化细胞并暴露于多个的系统 输入； （3）使用活细胞获得时间基因表达谱 已暴露于应力介质的组合混合物的阵列 密切模仿生理压力反应，并将这些信息用于 预测确定细胞恢复进展的分子事件 或压力期间的失败。该提案是一个跨学科项目 整合生物学，工程和计算的科学意见 方法。提案的每个要素都是整体成功不可或缺的一部分 项目，我们预计这将为您提供出色的培训 博士后研究生和研究生从事该项目。结果 应提供有关分子机制管理的有价值的新信息 代谢国家，将通过同行评审的出版物进行传播 在国家会议上的演讲。总而言之，拟议的工作试图 提供基本的研究和能够解决问题的人员基础 在复杂生物学现象的代谢工程等领域 正在调查。