Host-pathogen interactions in targeting Wolbachia to the stem cell niche

宿主-病原体相互作用将沃尔巴克氏体靶向干细胞生态位

基本信息

批准号：
7764790
负责人：
Horacio M Frydman
金额：
$ 10.8万
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：
2009
资助国家：
美国
起止时间：
2009-02-05 至 2012-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Although Wolbachia infections are found in most Arthropods and are of clinical importance in many parasitic diseases, very little is known about the cellular mechanisms responsible for their transmission. I have previously shown that Wolbachia preferentially populates the region of fly ovary containing the somatic stem cells, both in new inoculations and in established infected lines. Tropism for the somatic stem cell niche provides a previously undetected route to reach the germ line of new hosts. That the stem cell niche continues to be a site of accumulation suggests the possibility that horizontal and vertical transmission of Wolbachia may share common mechanisms. Here I propose to investigate the molecular and cellular mechanisms underlying host-pathogen interaction using this system. The goal of the proposal is to elucidate the bacterial and host factors involved in tropism for the stem cell niche. Towards this goal I will use molecular, genetic and cell biological tools available for Drosophila research. The questions that I intend to address are: 1. Manipulation of host cell processes: Effects of niche infection in stem cell activity 2. Interplay between bacteria and the host signaling system: Genetic disruption of signaling pathways controlling stem cell function 3. Evolutionary conservation of niche targeting: Identification of stem cell niche tropism in different host- parasite associations. 4. Determination of stem cell niche tropism: Investigation of host and bacterial factors. Layman summary: Wolbachia bacteria infect insects and other invertebrates. They are associated with river blindness and other human diseases. The bacteria are maternally transmitted in the egg from one generation to the next. I have shown that Wolbachia injected into uninfected host target the stem cell niche region of the ovary, from where it can directly infect the germ line. The same route may be important for continued maintenance of the bacteria in long-term infections. Further investigation of such transmission routes should yield information on evolution and ecology of this bacterial parasite, as well as cell biological strategies for pest and disease control.

描述（由申请人提供）：尽管在大多数节肢动物中都发现了沃尔巴氏菌感染，并且在许多寄生疾病中具有临床重要性，但对导致其传播的细胞机制知之甚少。我先前已经表明，在新接种和已建立的感染线中，沃尔巴奇优先填充了含有体细胞细胞的卵形卵巢区域。体细胞细胞生态裂的热带主义提供了以前未发现的途径，以达到新宿主的种系。干细胞生态位继续是一个积累部位，这表明沃尔巴基亚的水平和垂直传播可能具有共同的机制。在这里，我建议研究使用该系统相互作用的分子和细胞机制。该提案的目的是阐明干细胞生态裂涉及的向热带主义涉及的细菌和宿主因素。为了实现这一目标，我将使用可用于果蝇研究的分子，遗传和细胞生物学工具。我打算解决的问题是： 1。操纵宿主细胞过程：利基感染在干细胞活性中的影响 2。细菌与宿主信号系统之间的相互作用：控制干细胞功能的信号通路的遗传破坏 3。靶向利基靶向的进化保护：在不同宿主 - 寄生虫关联中的干细胞生态裂tropism的鉴定。 4。干细胞生态裂潮流的确定：宿主和细菌因子的研究。外行摘要： Wolbachia细菌感染昆虫和其他无脊椎动物。它们与河流失明和其他人类疾病有关。细菌在鸡蛋中从一代人传播到另一代。我已经证明，沃尔巴奇注射到未感染的宿主目标卵巢的干细胞生态位区域，从那里它可以直接感染细菌。相同的途径对于在长期感染中继续维持细菌可能很重要。对这种传播途径的进一步研究应产生有关该细菌寄生虫进化和生态学的信息，以及用于害虫和疾病控制的细胞生物学策略。