Underlying mechanisms of schistosome/snail compatibility

血吸虫/蜗牛相容性的潜在机制

基本信息

批准号：
7881838
负责人：
CHRISTOPHER JEFFREY BAYNE
金额：
$ 3.6万
依托单位：
OREGON STATE UNIVERSITY
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：
2009-08-14 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7881838
关键词：
Achievement Address Alleles Apoptosis Arginine Base Sequence Biomphalaria Breeding Cause of Death Cell physiology Cells Cognition Complex Country Cuprozinc Superoxide Dismutase Data Databases Distress Elements Encapsulated Event Exposure to Funding Future Gene Structure Generations Genes Genetic Genetic Polymorphism Genetic Transcription Genome Goals Grant Health Hemocytes Homologous Gene Human Hydrogen Peroxide Inbred Strain Individual Infection Interruption Intestinal Schistosomiases Investigator-Initiated Research Knowledge Laboratories Larva Learning Left Leukocytes Life Cycle Stages Messenger RNA Metabolism Methods Mission Modeling Molecular Natural Immunity Nitric Oxide Nitric Oxide Synthase Nitrogen Nucleic acid sequencing Oregon Outcome Oxidation-Reduction Oxygen Parasites Pathway interactions Peroxidases Phenotype Population Predisposition Prevention Process Production Property Proteins Quality of life Reactive Oxygen Species Reporter Research Research Personnel Research Project Grants Resistance Respiratory Burst Risk Role Schistosoma Schistosoma mansoni Schistosomatidae Schistosome Parasite Schistosomiasis Snails Social Welfare Sporocysts Staging Superoxides System Transcript Water Work arginase comparative enzyme activity experience functional genomics improved inhibitor/antagonist killings knowledge of results parasitism peroxiredoxin public health relevance response transmission process

Achievement Address Alleles Apoptosis Arginine Base Sequence Biomphalaria Breeding Cause of Death Cell physiology Cells Cognition Complex Country Cuprozinc Superoxide Dismutase Data Databases Distress Elements Encapsulated Event Exposure to Funding Future Gene Structure Generations Genes Genetic Genetic Polymorphism Genetic Transcription Genome Goals Grant Health Hemocytes Homologous Gene Human Hydrogen Peroxide Inbred Strain Individual Infection Interruption Intestinal Schistosomiases Investigator-Initiated Research Knowledge Laboratories Larva Learning Left Leukocytes Life Cycle Stages Messenger RNA Metabolism Methods Mission Modeling Molecular Natural Immunity Nitric Oxide Nitric Oxide Synthase Nitrogen Nucleic acid sequencing Oregon Outcome Oxidation-Reduction Oxygen Parasites Pathway interactions Peroxidases Phenotype Population Predisposition Prevention Process Production Property Proteins Quality of life Reactive Oxygen Species Reporter Research Research Personnel Research Project Grants Resistance Respiratory Burst Risk Role Schistosoma Schistosoma mansoni Schistosomatidae Schistosome Parasite Schistosomiasis Snails Social Welfare Sporocysts Staging Superoxides System Transcript Water Work arginase comparative enzyme activity experience functional genomics improved inhibitor/antagonist killings knowledge of results parasitism peroxiredoxin public health relevance response transmission process

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项目摘要

DESCRIPTION (provided by applicant): This revised proposal seeks support for an investigator-initiated research project into the cellular and molecular means used by intermediate hosts of a human parasite to immunologically attack and kill these parasites. The broad, long-term objective is to break the cycle of parasite transmission to at-risk human populations. The research builds on recent progress in the applicant's laboratory and other laboratories, and exploits the principles of comparative functional genomics and an emerging database for the host snail's genome. In particular, the research deals with genes, messenger RNAs and proteins involved in the cellular respiratory burst - a complex pathway in which damaging reactive oxygen and nitrogen species are produced by the defense cells of the host and which are at least partialy responsible for the capacity of individual snails to resist infection. The aims address plausible hypotheses dealing with (i) genes: details of gene structure, transcription and post-transcriptional editing, (ii) proteins (including enzyme activities), (iii) activation pathways for cell responses, and (iv) ultimate causes of death of sporocysts. The hypotheses are both tractable and reasonably anchored in already demonstrated phenomena. Experimental materials include individual Biomphalaria glabrata snails with known susceptible or resistant phenotypes to a standard strain (Oregon PR1) of Schistosoma mansoni, a causative agent of human intestinal schistosomiasis. Funds will enable a team of researchers to focus their efforts on these issues over 5 years. Knowledge resulting from the studies is expected to enhance the likelihood of achieving a mission of this agency - prevention of future transmission of schistosome parasites (S. mansoni) to humans - accomplished by interruption of the parasite's life cycle in its intermediate host, B. glabrata. These goals will be addressed using inbred strains of the intermediate host snail species for which we have the necessary genetic information (nucleic acid sequence data) and in which it is now feasible to use sensitive reporters for and efficient inhibitors of a variety of cell functions. PUBLIC HEALTH RELEVANCE: The burden of this (human blood-fluke) parasite is considerable among human populations in endemic regions (>70 countries in which ~200,000,000 people are infected). Infected individuals experience lower levels of cognition (it is harder to learn), and of energy to do physical work. Hence this work, in which the ultimate aim is to break the cycle of schistosome transmission, may contribute to public welfare through enhancement of health and of the quality of life (improved capacities to learn and to do physical work).

描述（由申请人提供）：该修订后的提案寻求对研究人员发动的研究项目的支持，以对人类寄生虫的中间寄主使用的细胞和分子手段进行免疫学攻击和杀死这些寄生虫。广泛的长期目标是打破寄生虫传播到处于危险中的人群的周期。该研究以申请人实验室和其他实验室的最新进展为基础，并利用了比较功能基因组学原理和宿主蜗牛基因组的新兴数据库。特别是，该研究涉及与细胞呼吸爆发有关的基因，信使RNA和蛋白质 - 一种复杂的途径，其中有害的活性氧和氮是由宿主的防御细胞产生的，并且至少是针对单个蜗牛抵抗感染的能力。该目的介绍了有关（i）基因的合理假设：基因结构，转录和转录后编辑的详细信息，（ii）蛋白质（包括酶活性），（iii）细胞反应的激活途径以及（IV）孢子细胞死亡的最终导致死亡。这些假设既可以说明，又合理地锚定在已经证明的现象中。实验材料包括具有已知易感性或抗性表型的单个生物掌labrata蜗牛，对人类肠道疾病的病原体（俄勒冈PR1）的标准菌株（俄勒冈PR1）。资金将使一群研究人员能够将他们的精力集中在5年的时间里。预计由研究产生的知识将增强实现该机构任务的可能性 - 预防将未来的血吸虫寄生虫（S。Mansoni）传播到人类中 - 通过中断寄生虫的生命周期在其中间宿主中的中断来实现。这些目标将使用中间宿主蜗牛物种的近交菌株来解决，我们为我们提供必要的遗传信息（核酸序列数据），并且现在可以使用敏感的记者来对各种细胞功能进行有效抑制剂。公共卫生相关性：该地区（人类血液）寄生虫的负担在流行地区的人口中相当大（> 70个国家感染了约20亿人口）。受感染的人经历较低的认知水平（很难学习）和进行体育工作的能量。因此，这项工作的最终目的是打破棘体传播的周期，可能通过增强健康和生活质量（提高学习和从事体育工作的能力）来促进公共福利。