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Molecular Studies of Immunoparasitology in Snails

蜗牛免疫寄生虫学的分子研究

基本信息

批准号：
7892908
负责人：
SI-MING ZHANG
金额：
$ 30.1万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-17 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7892908
关键词：
Affect Animals Antibodies Area Biomphalaria Cell Nucleus Chronic Complex Cytoplasm Data Defense Mechanisms Development Disease Electrophoretic Mobility Shift Assay Exposure to Fibrinogen Fresh Water Funding Gene Expression Gene Proteins Genome Goals Grant Human Immune Immune response Immunity Infection Knowledge Lead Life Cycle Stages Methods Molecular NF-kappa B National Center for Research Resources National Institute of Allergy and Infectious Disease Outcome Study Parasitic Diseases Pathway interactions Phylogenetic Analysis Play Proteins Recombinants Regulation Resistance Role STAT protein Schistosoma Schistosoma mansoni Schistosomatidae Schistosome Parasite Schistosomiasis Signal Pathway Signal Transduction Snails Staging Staining method Stains Testing Toll-like receptors base immune function improved novel strategies parent grant programs public health relevance research study response transcription factor transmission process

项目摘要

DESCRIPTION (provided by applicant): This is a competing supplemental application in response to the Enabling RPGs to Leverage NCRR Center and Center-like Programs. The proposal is made based on our recent data suggesting a role of immune signaling pathways in snail immune defenses. This proposed study extends the scope of my current three-year R01 grant (NIAID, #AI067686). Understanding the fundamental mechanisms of internal defense in the snail Biomphalaria glabrata may lead to new methods for blocking the transmission of schistosomiasis, a snail-borne disease that affects 200 million people worldwide. Immune signaling pathways are evolutionarily conserved and believed to control most immune-related gene expression. Transcription factors are the key molecules regulating a given pathway. The immune signaling pathways TLR (Toll-like receptor), Imd (Immune deficiency), and Jak (Janus kinas)/STAT (signal transducer and activator of transcription) regulated by nuclear factor-kappa B (NF-?B) and STAT transcription factors have been shown to play the central role in humoral and cellular immune responses. In spite of the enormous amount of data accumulated in a wide phylogenetic range of animals, nothing is known about the existence and function of these immune signaling pathways in B. glabrata. We have identified two NF-?Bs (BgRel and BgRelish) and two STATs (BgSTAT1 and 2) from B. glabrata and examined their expression. Based on our preliminary data, we hypothesize that TLR, Imd, and Jak/STAT pathways are conserved in B. glabrata in terms of functionality. To test our hypothesis, we propose to investigate whether TLR, Imd, and Jak/STAT signaling pathways are activated in snails after exposure to S. mansoni. The outcome of this study may open a new area in the studies of snail immune signal transduction, which should improve our understanding of snail immunity and ultimately benefit the long-term goal of schistosomiasis control. PUBLIC HEALTH RELEVANCE: This proposed study will help us in better understanding the fundamental mechanisms of the internal defenses of the snail Biomphalaria glabrata, the intermediate host of human blood fluke Schistosoma mansoni. This may lead to new methods for blocking the transmission of Schistosomiasis, a snail-borne disease that affects 200 million people worldwide.

描述（由申请人提供）：这是一项竞争性补充申请，旨在响应“使 RPG 能够利用 NCRR 中心和类似中心的计划”。该提议是根据我们最近的数据提出的，这些数据表明免疫信号通路在蜗牛免疫防御中的作用。这项拟议的研究扩展了我当前三年 R01 资助的范围（NIAID，#AI067686）。了解光滑双脐蜗牛内部防御的基本机制可能会带来阻止血吸虫病传播的新方法，血吸虫病是一种蜗牛传播的疾病，影响着全世界 2 亿人。免疫信号通路在进化上是保守的，并且被认为控制着大多数免疫相关基因的表达。转录因子是调节给定途径的关键分子。由核因子-κB (NF-κB) 和 STAT 转录因子调节的免疫信号通路 TLR（Toll 样受体）、Imd（免疫缺陷）和 Jak（Janus kinas）/STAT（信号转导和转录激活因子）已被证明在体液和细胞免疫反应中发挥核心作用。尽管在广泛的动物系统发育范围内积累了大量数据，但对光滑拟杆菌中这些免疫信号通路的存在和功能一无所知。我们从光滑拟杆菌中鉴定出两种 NF-κB（BgRel 和 BgRelish）和两种 STAT（BgSTAT1 和 2），并检查了它们的表达。根据我们的初步数据，我们假设 TLR、Imd 和 Jak/STAT 途径在光滑 B. glabrata 中在功能上是保守的。为了检验我们的假设，我们建议研究在接触曼氏链螺后，蜗牛中的 TLR、Imd 和 Jak/STAT 信号通路是否被激活。这项研究的结果可能会开辟蜗牛免疫信号转导研究的新领域，这将提高我们对蜗牛免疫的认识，最终有利于血吸虫病控制的长期目标。公共健康相关性：这项拟议的研究将帮助我们更好地了解光滑双脐蜗牛（人类血吸虫曼氏血吸虫的中间宿主）内部防御的基本机制。这可能会带来阻止血吸虫病传播的新方法，血吸虫病是一种蜗牛传播的疾病，影响着全世界 2 亿人。