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Functional genomics for Chlamydia

衣原体功能基因组学

基本信息

批准号：
10464275
负责人：
P Scott Hefty
金额：
$ 81.08万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10464275
关键词：
Achievement Acute Address Alleles Area Bacteria Biological Biological Models Biology Cells Characteristics Chimera organism Chlamydia Chlamydia Infections Chlamydia muridarum Chlamydia trachomatis Complex Defect Development Essential Genes Female Female genitalia Foundations Generations Genes Genetic Genetic Determinism Genetic study Genome Goals Growth Growth and Development function Horizontal Gene Transfer Human Hybrids In Vitro Infection Influentials Interferon Type II Investigation Knowledge Lead Libraries Maps Mediating Medical History Membrane Membrane Proteins Modeling Modernization Molecular Mus Mutagenesis Natural History Nature Organism Outcome Pathogenesis Pathology Pathway interactions Phase Phenotype Play Prevention strategy Proteins Reproductive Health Research Personnel Role Series Sexually Transmitted Diseases Shapes System Technology Technology Transfer Tropism Ubiquitin Virulence Virulence Factors Work acute infection clinically relevant cohort design experience experimental study functional genomics gene product genetic manipulation genome-wide human pathogen in vitro Assay in vivo innovation interest microorganism mouse model mutant novel therapeutics pathogen pathogenic bacteria pressure protein function reproductive reproductive tract tool

项目摘要

PROJECT SUMMARY For bacterial pathogens, the first studies that begin to define the microorganism’s functional genetic nature on a genome-wide scale, frequently represent a landmark and highly impactful achievement. The major human pathogen Chlamydia trachomatis is a bacterium for which such studies have not been performed, in large part due to Chlamydia’s obligate intracellular nature and historical intractability to modern genetic manipulation. With the development of two major genetic tools for Chlamydia by our group—transposon mutagenesis and lateral gene transfer chimeras—functional genomic investigations in Chlamydia are now possible. Our long term goal is to globally define and functionally characterize the genetic correlates to C. trachomatis infection and pathogenesis. Using the complementary approaches of transposon mutagenesis and interspecies chimeras, we propose to: (i) identify the major genetic determinants of Chlamydia infection using a clinically relevant mouse model and in vitro assays; (ii) determine the Chlamydia genes associated with host adaptation by exploiting interspecies lateral gene transfer within Chlamydia and the signature host tropisms of the parental strains; (iii) characterize the mechanisms of host cell subversion by the secreted inclusion membrane effector proteins IncU and IncS. These efforts are essential for gaining a functional appreciation of the role that unique chlamydial genes play in the organism’s growth and development, and also Chlamydia’s evolutionary adaptation to successfully maintain infection and pathogenesis in complex mammalian hosts. We anticipate that Chlamydia will serve as a model obligate intracellular bacterium, and, therefore, the knowledge obtained from this work will broadly extend to other pathogens that have evolved an obligate intracellular niche in their mammalian hosts. Identification of these loci is critical for our understanding of the mechanisms through which Chlamydia have adapted to mammalian hosts, and represents an important step towards elucidating the major virulence correlates of C. trachomatis in humans.

项目总结