Manipulation of stem cell activity and cell death by intracellular bacteria

细胞内细菌操纵干细胞活性和细胞死亡

基本信息

批准号：
8711667
负责人：
Horacio M Frydman
金额：
$ 38.47万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-07 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8711667
关键词：
Address Adult Aedes Affect Apoptosis Bacteria Biological Biology Blood Candidate Disease Gene Cause of Death Cell Cycle Cell Death Cell Proliferation Cell physiology Cells Chickens Communicable Diseases Confocal Microscopy Culex pipiens Culicidae Databases Dengue Development Developmental Process Disease Disease Vectors Down-Regulation Drosophila genus Event Fertility Foundations Future Gene Expression Genetic Genomics Germ Cells Goals Helminths Human Image Analysis Immunity Infection Insecta Invaded Knowledge Label Longevity Measures Mitosis Mitotic Activity Modeling Molecular Molecular Profiling Morbidity - disease rate Nature Nematoda Oogenesis Organism Ovary Pathway interactions Phenotype Plasmodium Population Production Property Regulation Reproduction Research Role Sorting - Cell Movement Stem cells Symbiosis System Testing Transgenic Organisms Tropism Up-Regulation West Nile virus Wolbachia bacterial vector base chikungunya density disease transmission disorder control egg experience feeding fly male mortality novel novel strategies pathogen reproductive stem cell biology stem cell division stem cell niche tool transmission process vector control

项目摘要

DESCRIPTION (provided by applicant): Infections of the maternally transmitted intracellular bacteria Wolbachia are widespread in nature, found in most insects and in parasitic worms. Many insects that harbor these bacteria are the vectors of devastating human infectious diseases. The biology at the interface between Wolbachia and their hosts offers novel strategies for the control of disease vectors. Fruit fly Wolbachia strains can invade and sustain themselves in mosquito populations, reduce adult lifespan, affect mosquito reproduction and inhibit the ability of several pathogens to infect mosquitoes, including Dengue, Chikungunya, West Nile Virus, and both chicken and human plasmodium. Nevertheless, very little is known about the mechanistic basis for Wolbachia-insect host interactions, limiting the capability of fully exploitig Wolbachia's biology towards control efforts. The goal of this application is to investigate the cellular and molecular mechanisms of Wolbachia manipulation of insect reproduction. Wolbachia often alter their host's reproductive ability; yet, very little is known about how this i achieved. We identified the developmental processes that Wolbachia interfere with to increase the levels of host egg production. Wolbachia maternal transmission is enhanced by bacterial inhibition of germ cells death during egg production. Furthermore, Wolbachia can upregulate the rate of proliferation of the germline stem cells, further increasing transmission of bacteria via te egg. To dissect the cellular and molecular mechanisms of these novel host manipulations, we will: 1. Determine the effects of different Wolbachia strains in germline programmed cell death in D. melanogaster, Culex pipiens and Aedes aegypti. 2. Investigate the effect of infection on stem cell division with different Wolbachia strain-host species. 3. Determine Wolbachia-induced differences in the transcriptional profile that affect stem cell proliferation. Our studies of Wolbachia interaction with their hosts at the cellular and molecular level will yield valuable new information on basic biology of symbiotic interactions during oogenesis. This fundamental knowledge provide the foundation for the development of new cell biological and Wolbachia based strategies for disease control. Furthermore, Wolbachia interaction with stem cell niches and manipulation of stem cell proliferation will expand our basic understanding of the properties of stem cell niches and how they control stem cell proliferation.

描述（由申请人提供）：在大多数昆虫和寄生蠕虫中发现的母体传播细胞内细菌的感染在自然界中是广泛的。藏有这些细菌的许多昆虫是毁灭性人类传染病的媒介。 Wolbachia及其宿主之间界面的生物学为控制媒介的控制提供了新的策略。果蝇Wolbachia菌株可以在蚊子种群中侵袭和维持自己，减少成人寿命，影响蚊子的繁殖并抑制几种病原体感染蚊子的能力，包括登革热，基孔肯尼亚，西尼罗河病毒，以及鸡和人类疟原虫。然而，关于沃尔巴基亚体内宿主相互作用的机械基础知之甚少，这限制了完全剥削的沃尔巴基亚生物学对控制工作的能力。该应用的目的是研究Wolbachia操纵昆虫繁殖的细胞和分子机制。沃尔巴奇经常改变宿主的生殖能力。然而，关于我如何实现的知之甚少。我们确定了Wolbachia干扰以增加宿主产卵水平的发育过程。在产卵过程中，细菌对生殖细胞死亡的细菌抑制作用增强了沃尔巴氏菌的传播。此外，Wolbachia可以上调种系干细胞的增殖速率，从而进一步增加细菌通过TE卵的传播。为了剖析这些新型宿主操纵的细胞和分子机制，我们将：1。确定wolbachia菌株在生殖线程序中不同的wolbachia菌株在D. melanogaster，Culex pipiens和aedees aeegypti中的影响。 2。研究感染对不同沃尔巴氏菌菌株宿主物种的干细胞分裂的影响。 3。确定沃尔巴奇诱导的影响干细胞增殖的转录特征的差异。我们对Wolbachia在细胞和分子水平上与宿主相互作用的相互作用的研究将产生有关卵子发生过程中共生相互作用的基本生物学的有价值的新信息。这种基本知识为开发基于疾病控制的新细胞生物学和沃尔巴氏菌策略奠定了基础。此外，Wolbachia与干细胞壁ni的相互作用和对干细胞增殖的操纵将扩大我们对干细胞壁ches性质的基本理解以及它们如何控制干细胞增殖。