GENOMICS OF HIGH TEMPERATURE BIOLOGICAL SYSTEMS

描述(改编自调查员摘要)：许多成员 第三个王国，古生代，是极端嗜热生物，能够在 某些情况下，气温高达113摄氏度。其中许多 微生物有大约200万个碱基对的小基因组，以及 来自系统发育树的更深层次的分支，与 认为最古老的祖先微生物在高处生长 温度。它们提出了有趣的分子基础问题 生物学，因为它们的所有生命过程都发生在高温下。 例如，DNA如何高保真地复制，以及这些 生物避免了由于热诱导的DNA损伤而导致的过度突变，以及 他们有维修系统吗？调控蛋白如何识别和结合 温度在100摄氏度以上的操作员？染色体是如何 保持稳定？蛋白质是如何在如此高温下发挥作用的？ 这些和其他细胞过程的新策略将会被发现 随着我们增加对极端嗜热者的研究？米勒博士建议 为了对其中一种生物进行功能性基因组分析， 一种可以在103℃生长的古生代嗜氧性焦杆菌，并与 功能基因组与其他高温微生物的关系。 他与梅尔·西蒙博士在加州理工大学的实验室合作， 完成了焦杆菌2.2兆碱基全基因组的测序 好氧菌。他将使用这个序列，他正在进行 注释，作为该微生物基因组研究的起点。 他将采用全基因组的基因表达体外分析，并将 开发基因系统，以允许更多的分析方法 使用。调查人员还将开始一些比较研究， 能够在113摄氏度下生长的已知最高温度--烟腐病菌的基因组 任何活着的有机体的温度。

DESCRIPTION (adapted from investigator's abstract): Numerous members of the third kingdom, Archaea, are extreme hyperthermophiles, able to grow at temperatures up to 113 degrees C in some cases. Many of these microorganisms have small genomes, on the order of 2 million base pairs, and are from the deeper branches of the phylogenetic tree, in agreement with the notion that the most ancient ancestral microorganisms grew at high temperatures. They pose interesting fundamental questions in molecular biology, since all of their life processes occur at elevated temperatures. For instance, how can the DNA replicate with high fidelity, and how do these organisms avoid excessive mutation due to heat-induced DNA lesions, and what repair systems do they have? How do regulatory proteins recognize and bind to operators at temperatures above 100 degrees C? How does the chromosome remain stable? How are proteins able to function at such high temperatures? What new strategies for these and other cellular processes will be uncovered as we increase our study of extreme hyperthermophiles? Dr. Miller proposes to develop a functional genomic analysis of one of these organisms, Pyrobaculum aerophilum, an Archaeon that can grow at 103 C, and to compare aspects of the functional genome with other high temperature microorganisms. He has, in collaboration with Dr. Mel Simon's laboratory at CalTech, completed the sequence of the entire 2.2 megabase genome of Pyrobaculum aerophilum. He will use this sequence, which he is in the process of annotating, as a starting point for genomic studies of this microorganism. He will employ genome wide in vitro analyses of gene expression, and will develop a genetic system to permit additional methods of analysis to be used. The investigator will also begin some comparative studies on the genome of Pyrolobus fumarii, which can grow at 113 C, the highest known temperature for any living organism.