Pathoadaptive Mutations in Treponema Pallidum, the Syphilis
梅毒螺旋体的病理适应性突变
基本信息
- 批准号:8303036
- 负责人:
- 金额:$ 19.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-03-01 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressArchivesCentral Nervous System InfectionsClinicalCodeCollectionDNADatabasesDevelopmentEpidemiologyFingerprintFoundationsFutureGene MutationGene SilencingGenesGeneticGenetic VariationGenomeGenomicsGeographic LocationsGlobus PallidusGoalsHot SpotHumanImmune responseImmunologyIndividualIntercistronic RegionKnowledgeLaboratoriesMapsMethodsModelingModificationMolecularMolecular ProfilingMutationNeuraxisNeurosyphilisNucleotidesOrder SpirochaetalesOrganismOryctolagus cuniculusPathogenesisPatientsPhylogenetic AnalysisPhylogenyPopulationPositioning AttributeProteinsPublic HealthResearchSamplingSexually Transmitted DiseasesSourceSpecificitySyphilisTechniquesTestingTissuesTranscriptTreponema pallidumVariantVirulentWorkbasebody systemclinical phenotypecomparativecomparative genomicscross immunitygenetic manipulationgenome sequencinggenome wide association studygenome-widegenome-wide analysisglobal healthinsightnovel
项目摘要
DESCRIPTION (provided by applicant): Syphilis is a significant problem for global health. It is caused by Treponema pallidum subsp. pallidum (T. palidum), a highly virulent, invasive and intractable spirochete. The goal of this proposal is to use comparative genomics on a population-wide scale to determine the contribution of genetic mutations to the identification of T. pallidum strains associated with distinct tissue enrichments, to the development of a refined strain fingerprinting method and for genome-wide expression profiling. Comparative genome-wide analysis will be done on a number of T. pallidum isolates as well as more recent isolates originated from patients with distinct clinical presentations and diverse geographical distributions.
The Specific Aims are as follows: 1. Determine the population genomic variability of T. pallidum isolates representing geographical and chronological diversity; 2. Identify repeated mutational changes (hot spot mutations) in T. pallidum. High-throughput de novo, state-of-the-art sequencing approaches will be used to obtain a comprehensive number of genome sequences from our collection of T. pallidum isolates. We will create a publicly available database that will include a genome-wide map of mutations acquired in T. pallidum. Targeted qRT-PCR analysis will be performed to determine impact of hot spots on transcript levels of selected genes.
Overall, accomplishment of the proposed studies will set the basis for the advance of our understanding at the molecular level of the epidemiology of T. pallidum isolates. It will also lay the groundwork for futures studies on a large scale, population-wide association research between specific genetic variations and tissue/organ/system involvement, and for a better understanding at the molecular level of how treponemes can, for example, re-infect or super-infect individuals. These studies can have a far reaching impact on issues of clinical and public health significance.
PUBLIC HEALTH RELEVANCE: Understanding the mechanisms Treponema pallidum uses to cause different clinical presentations and how this organism can re-infect or super-infect an individual will have a significant impact on public health. Furthermore, the studies will help to understand the epidemiology of syphilis.
描述(由申请人提供):梅毒是全球健康的重要问题。它是由treponema pallidum subsp引起的。 Pallidum(T. palidum),一种高毒,侵入性和顽固性的螺旋体。该提案的目的是在人群范围内使用比较基因组学来确定基因突变对与不同组织富集相关的pallidum菌株鉴定的贡献,以及开发精炼菌株的指纹方法和对全基因组表达谱的开发。比较全基因组的分析将对许多T. pallidum分离株以及最新的分离株进行,起源于具有不同临床表现和不同地理分布的患者。
具体目的如下:1。确定代表地理和时间顺序多样性的粒细胞分离株的种群基因组变异性; 2。识别甲状腺抗体的重复突变变化(热点突变)。从头开始,最先进的测序方法将用于从我们的T. pallidum分离株的集合中获取综合数量的基因组序列。我们将创建一个公开可用的数据库,其中包括在T. pallidum中获得的全基因组突变图。将进行有针对性的QRT-PCR分析,以确定热点对选定基因的转录水平的影响。
总体而言,拟议研究的完成将为我们在粒细胞分离株的流行病学的分子水平上的理解发展树立基础。它还将为期货研究奠定基础,以大规模的人口遗传变异与组织/器官/系统的参与之间的研究,并在分子水平上更好地理解treponemes如何重新感染或超级感染者。这些研究可能会对临床和公共卫生意义问题产生巨大影响。
公共卫生相关性:了解Treponema Pallidum用来引起不同的临床表现的机制,以及该生物如何重新感染或超级感染者将对公共卫生产生重大影响。此外,研究将有助于理解梅毒的流行病学。
项目成果
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{{ truncateString('GLABER ARTURO CENTURION-LARA', 18)}}的其他基金
Placental Colonization by Treponema Pallidum, Congenital Syphilis & Novel Vaccine
梅毒螺旋体、先天性梅毒的胎盘定植
- 批准号:
8819224 - 财政年份:2015
- 资助金额:
$ 19.29万 - 项目类别:
Placental Colonization by Treponema Pallidum, Congenital Syphilis & Novel Vaccine
梅毒螺旋体、先天性梅毒的胎盘定植
- 批准号:
9197601 - 财政年份:2015
- 资助金额:
$ 19.29万 - 项目类别:
Placental Colonization by Treponema Pallidum, Congenital Syphilis & Novel Vaccine
梅毒螺旋体、先天性梅毒的胎盘定植
- 批准号:
9128553 - 财政年份:2015
- 资助金额:
$ 19.29万 - 项目类别:
EXPRESSION AND FUNCTION OF MSP HOMOLOGUES IN T PALLIDUM
MSP 同源物在 T Pallidum 中的表达和功能
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6332444 - 财政年份:2000
- 资助金额:
$ 19.29万 - 项目类别:
EXPRESSION AND FUNCTION OF MSP HOMOLOGUES IN T PALLIDUM
MSP 同源物在 T Pallidum 中的表达和功能
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6167432 - 财政年份:1999
- 资助金额:
$ 19.29万 - 项目类别:
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Pathoadaptive Mutations in Treponema Pallidum, the Syphilis
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