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Drosophila melanogaster as a model organism to study Chlamydia trachomatis early effectors

果蝇作为模式生物研究沙眼衣原体早期效应子

基本信息

批准号：
10115601
负责人：
Travis James Jewett
金额：
$ 18.63万
依托单位：
UNIVERSITY OF CENTRAL FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10115601
关键词：
Actins Animal Model Apical Bacteria Bacterial Genes Bacterial Proteins Binding Biochemical Biological Metamorphosis Biology Bundling Cell model Cells Cellular biology Chlamydia Chlamydia trachomatis Collection Cytology Cytoskeleton Data Defect Development Disease Dissection Drosophila genus Drosophila melanogaster Environment Epithelial Epithelial Cells Event Extracellular Space F-Actin Foundations Genetic Goals Growth High Prevalence Human In Vitro Individual Infection Interruption Learning Mediating Membrane Microscopic Modeling Molecular Pathogenesis Perivitelline Space Phenotype Phosphorylation Prevention Proteins Research Proposals Sexual Transmission Sexually Transmitted Diseases Signal Pathway Signal Transduction Structure Tertiary Protein Structure Tissues Transgenic Organisms United States Work base cellular microvillus egg fly human tissue in vivo innovation insight monolayer mutant novel therapeutic intervention pathogen polarized cell programs protein function src-Family Kinases young woman

项目摘要

SUMMARY: We aim to learn how Chlamydia trachomatis secreted effectors direct cellular changes both individually and cooperatively within fruit flies (Drosophila melanogaster). Our preliminary data indicate that expression of chlamydial Tarp in flies leads to both macroscopic (curled bristles) and microscopic (irregular microvilli) developmental defects. The fruit fly model organism contains well defined polarized cells and developmental programs which can be quantitatively evaluated. This level of precision in a polarized cell model allows for the molecular dissection of individual C. trachomatis effectors and assessment of effector cooperation which has not yet been investigated. Known targets of the early C. trachomatis effectors such as actin, Crk adapters, Src tyrosine kinases, and PI3K are conserved in the fruit fly model suggesting cellular changes observed in flies are likely to mimic the effects on human tissues. In the short term, we believe that the fruit fly model will provide mechanistic insight into chlamydial effector directed host pathogen interactions and in the long term may serve as a powerful platform to explore bacterial genes of unknown function. Elucidation of the molecular mechanisms employed by C. trachomatis to initiate a successful infection may provide clues that can be applied to novel therapeutic interventions for this prolific pathogen.

总结：我们的目标是了解沙眼衣原体分泌的效应子如何单独和果蝇（Drosophila melanogaster）。我们的初步数据表明，衣原体Tarp在苍蝇导致宏观（卷曲的刚毛）和微观（不规则的微绒毛）发育缺陷果蝇模式生物体含有明确的极化细胞和发育细胞。可以进行定量评估的项目。极化细胞模型中的这种精度水平允许对单个C.沙眼效应器和评估效应器的合作，尚未被调查。早期C.沙眼效应物，如肌动蛋白、Crk衔接子、Src 酪氨酸激酶和PI3K在果蝇模型中是保守的，表明在果蝇中观察到的细胞变化很可能会模仿对人体组织的影响。在短期内，我们认为果蝇模型将为衣原体效应子导向的宿主病原体相互作用提供了机制性的见解，这可能是探索未知功能的细菌基因的有力平台。分子解析 C.采用的机制沙眼衣原体启动成功感染可能提供线索，应用于这种多产病原体的新型治疗干预。