Molecular Studies of Immunoparasitology in Snails

蜗牛免疫寄生虫学的分子研究

• 批准号: 7433830
• 负责人: SI-MING ZHANG
• 金额: $ 36.79万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7433830
• 关键词: Address; Affect; Antibodies; Area; Binding; Binding Proteins; Biological Models; Biomphalaria; Blood Proteins; Brazil; Compatible; Complement; Development; Disruption; Ensure; Exposure to; Fibrinogen; Fresh Water; Gene Proteins; Genes; Genetic Recombination; Goals; Gram-Negative Bacteria; Growth; Health; Helminths; Homologous Gene; Human; Immune; Immunity; In Vitro; Infection; Invertebrates; Investigation; Lead; Learning; Longevity; Methods; Molecular; Mutation; Nature; Numbers; Outcome; Output; Parasites; Pathway interactions; Play; Point Mutation; Predisposition; Proteins; RNA Interference; Recombinant Proteins; Recombinants; Relative (related person); Reporting; Research Personnel; Resistance; Resistance to infection; Role; Schistosoma; Schistosoma mansoni; Schistosomatidae; Schistosome Parasite; Schistosomiasis; Snails; Sporocysts; Study models; System; Techniques; Testing; Thinking; Toxic effect; Work; defense response; experience; in vivo; innovation; insight; novel; peptidoglycan recognition protein; prevent; programs; receptor; reproductive; resistance mechanism; response; schistosomin; snail protein; success; transmission process

DESCRIPTION (provided by applicant): The freshwater snail Biomphalaria glabrata plays an indispensible role in transmission of the human blood fluke, Schistosoma mansoni. Increasing our understanding of the fundamental mechanisms of internal defense of this snail could help develop novel methods of control of schistosomiasis which still infects 200 million people world-wide. Much remains unknown regarding the molecular interplay between schistosomes and their snail hosts, and the B. glabrata - S. mansoni model system is by far the best for assessing underlying mechanisms of resistance and compatibility. The proposed investigations are built on previous studies suggestive of a functional role of snail blood proteins called FREPs (fibrinogen-related proteins) in anti-schistosome defenses. They are further inspired by our discoveries showing that B. glabrata generates a surprising diversity of FREP genes through point mutation and recombination, a discovery that along with work in other labs has provoked a general reconsideration of the capacity of invertebrates to generate diversified defense responses. In this application, which has been extensively revised in response to the previous review, we develop a general approach for assessing the functionality of putative immune effectors (FREPs are the main, but not the sole, effectors available to be tested using this approach) in influencing the ability of S. mansoni to develop successfully in B. glabrata. In so doing, it is important to examine candidate effector molecules both from the perspective of their involvement in resistance to infection, and as general determinants of compatibility. Specifically, we will further develop RNA interference (RNAi) and recombinant protein/antibody approaches to examine the functional role of FREPs in affecting the development of parasites in incompatible hosts, using both in vivo and in vitro approaches. Other candidates we have recently identified, namely gram-negative bacteria binding protein (GNBP) and peptidoglycan recognition proteins (PGRPs), the snail homologs of key molecules controlling upstream Toll/Imd pathways, are also available for study, thus further broadening our understanding of snail immunity. Finally, we will attempt to disrupt the successful parasitization of compatible snails by S. mansoni. The ability to effect such disruption would be an important advance because compatibility ensures the continued transmission of schistosomiasis in endemic areas. This study will enable us to gain valuable insights into the functionality of FREPs and other candidates, and even more importantly, to develop a system of general applicability for evaluating the role of any snail candidate molecules in influencing the outcome of an encounter between S. mansoni and its snail host.

描述（由申请人提供）：淡水蜗牛生物掌lia glabrata在人类血液氟的传播中起着不可或缺的作用，曼森Scistosoma。越来越多地了解这种蜗牛内部防御的基本机制可能有助于开发新颖的控制血吸虫病方法，这些方法仍然会感染全球2亿人。关于血吸虫与其蜗牛宿主之间的分子相互作用以及B. glabrata -S。Mansoni模型系统是迄今为止评估抗药性和兼容性基本机制的最佳方法。拟议的研究是基于先前的研究，提示蜗牛血蛋白在抗速肌防御措施中称为FREP（纤维蛋白原相关的蛋白）的功能作用。它们进一步启发了我们的发现，表明B. glabrata通过点突变和重组产生了FREP基因的令人惊讶的多样性，这一发现与其他实验室的工作一起引发了对无脊椎动物产生多元化防御反应的能力的一般重新考虑。在此应用程序中，对先前的综述进行了广泛的修订，我们开发了一种评估推定免疫效应子功能的通用方法（FREP是主要的，但不是唯一的，使用这种方法测试的效应子）来影响S. Mansoni在B. Glabrata中成功发展的能力。这样一来，重要的是要从候选效应分子从参与抵抗感染的角度以及作为兼容性的一般决定因素。具体而言，我们将进一步开发RNA干扰（RNAI）和重组蛋白/抗体方法，以使用体内和体外方法来检查FREP在影响不相容宿主中寄生虫发展的功能作用。我们最近确定的其他候选者，即革兰氏阴性细菌结合蛋白（GNBP）和肽聚糖识别蛋白（PGRP），控制上游/IMD途径的关键分子的蜗牛同源物也可以进行研究，从而进一步扩大我们对蜗牛免疫力的了解。最后，我们将尝试破坏S. Mansoni的兼容蜗牛的成功寄生。实现这种干扰的能力将是一个重要的进步，因为兼容性确保了血吸虫病在地方性地区的持续传播。这项研究将使我们能够对FREP和其他候选者的功能获得宝贵的见解，甚至更重要的是，开发了一种一般适用系统，以评估任何蜗牛候选分子在影响S. Mansoni及其蜗牛宿主之间相遇结果中的作用。