GENETIC ORGANIZATION OF TREPONEMA DENTICOLA
GENETIC ORGANIZATION OF TREPONEMA DENTICOLA
批准号:
2897187
负责人:
GEORGE M WEINSTOCK
金额:
$68.92万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-07-01 至 2001-06-30
中文摘要
描述(改编自《调查员摘要》):该项目将
测定齿密螺旋体染色体DNA序列
人类重要的口腔病原体,与牙周炎有关。牙周
感染影响到很大一部分人口,导致显著的
医疗费用。此外,这种细菌是为数不多的螺旋体之一
可以在动物外培养,提供了一个有吸引力的系统
用来研究这些有机体。最近的靶向突变和基因
转移已经应用于齿纹夜蛾,使其成为一种选择的有机体。
这种方法应该允许牙周感染的作用和机制
由T.denticola提出,有待详细定义。基因组DNA序列和作图
克隆将为这项研究提供巨大的资源。齿纹夜蛾
基因组为3Mb的环状染色体。确定它的DNA序列是
这一分析的下一个合乎逻辑的步骤。随着DNA的最新发展
测序技术,以及这些进展在
其他细菌基因组序列的测定,一种齿状毛滴虫
基因组计划现在是可行的。
基因组的完整DNA序列将通过测序完成
在24,000个质粒克隆中的插入片段末端。此外,600年末
将对大插入的lambda和BAC克隆进行测序,以提供更多
结案的资源。这不仅将产生基因组序列,而且
还将提供一组跨越基因组的克隆图谱。相似之处
与序列数据库中的已知基因之间的关系将是
通过计算机搜索识别(例如,使用BLAST程序)。这
方法给出了许多重要问题的直接答案,例如
Ditticola的代谢能力,因为序列相似性是
在这些蛋白质中非常保守。此外,具有以下功能的函数
将确定与已知毒力因子的序列相似性。这些
可以很容易地作为进一步研究的目标,因为相关克隆将
可用。还将为该项目开发一个基因组数据库,其中
将在互联网上提供,使研究人员能够评估大型
有关序列、功能、克隆和其他物理信息的信息量
将生成的地图要素。
英文摘要
DESCRIPTION (Adapted from the Investigator's Abstract): This project will
determine the DNA sequence of the chromosome of Treponema denticola, an
important oral pathogen of man, associated with periodontitis. Periodontal
infection affects a large segment of the population resulting in significant
health costs. In addition, this bacterium is one of the few spirochetes
that can be cultured outside of animals, providing an attractive system in
which to study these organisms. Recently targeted mutagenesis and gene
transfer have been applied to T. denticola, making it an organism of choice.
This approach should allow the role and mechanisms of periodontal infection
by T. denticola to be defined in detail. A genomic DNA sequence and mapped
clones would provide a tremendous resource for this study. The T. denticola
genome is a 3 Mb circular chromosome. Determining its DNA sequence is the
next logical step in this analysis. With the recent developments in DNA
sequencing technology, and the application of these advances to
determination of the sequence of other bacterial genomes, a T. denticola
genome project is now feasible.
The complete DNA sequence of the genome will be accomplished by sequencing
the ends of inserts in 24,000 plasmid clones. In addition, the ends of 600
large insert lambda and BAC clones will be sequenced to provide additional
resources for closure. This will not only produce the genomic sequence, but
also will provide a mapped set of clones spanning the genome. Similarities
between T. denticola sequences and known genes in sequence databases will be
identified by computer searches (e.g., using the BLAST program). This
approach gives immediate answers to a number of important questions such as
the metabolic capabilities of T. denticola, since sequence similarities are
well conserved among these proteins. In addition, functions that have
sequence similarity to known virulence factors will be identified. These
can be readily targeted for further study since the relevant clones will be
available. A genome database will also be developed for this project, which
will be available on the Internet allowing researchers to assess the large
amount of information on sequences, functions, clones, and other physical
map features that will be generated.
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