Mali ICEMR Project 2: Immunogenomics Epidemiology of Malaria in Mali

马里 ICEMR 项目 2：马里疟疾的免疫基因组学流行病学

• 批准号: 10381468
• 负责人: MAHAMADOU DIAKITE
• 金额: $ 5.6万
• 依托单位: UNIV OF SCIENCES, TECH & TECH OF BAMAKO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-18 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381468
• 关键词: Affect; Africa; African; Alleles; Anti-malarial drug resistance; Antimalarials; Area; Artemisinins; Blood; Candidate Disease Gene; Catalogs; Cell physiology; Cellular Structures; Clinical; Code; Combined Modality Therapy; Coupled; Disease Outcome; Drug resistance; Effectiveness; Enzymes; Epidemiology; Erythrocytes; Ethnic group; Evolution; Failure; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genetic Variation; Genetic study; Genome; Goals; Human; Human Genetics; Immune; Immune system; Immunity; Immunogenomics; Immunologics; Infection; Informatics; Interdisciplinary Study; Linkage Disequilibrium; Malaria; Malaria Vaccines; Mali; Measurement; Measures; Metabolic; Metabolism; Microarray Analysis; Modeling; Molecular; Monitor; Mutation; Parasite resistance; Parasites; Pattern; Persons; Pharmaceutical Preparations; Phenotype; Plasmodium; Plasmodium falciparum; Plasmodium falciparum genome; Population; Population Group; Population Study; Predisposition; Prevention; Preventive treatment; Process; RNA; Regulation; Research; Resistance; Resistance development; Resolution; Seasons; Site; Southeastern Asia; Stream; Structure; Surveillance Methods; Treatment Efficacy; Treatment outcome; Variant; chemotherapy; clinical phenotype; community living; data exchange; density; diagnostic strategy; drug metabolism; genetic analysis; genomic variation; malaria transmission; molecular diagnostics; molecular marker; neglect; next generation sequencing; novel; response; statistics; transmission process; treatment response

This Project of the ICEMR focuses on genetic variation in the malaria parasite and human host, and their impact on malaria transmission and effectiveness of malaria control measures in four sites in Mali, West Africa. Recent advances in genome research provide unprecedented opportunities to tackle questions that decades of immunological research have failed to resolve, such as how people naturally clear malaria parasites from the blood stream or why some people get severe malaria. By investigating how the natural genetic variation in humans and parasites affects malaria susceptibility, and efforts to control malaria, we can build a catalogue of host/parasite molecules that are critical for protective immunity. Recently, Plasmodiun falciparum has developed resistance to the artemisinins, the most effective antimalarial drugs, and the continued evolution of its genome is a major obstacle to malaria control. Now, next generation sequencing approaches coupled with advances in statistics and informatics have transformed our ability to study genetic variation in Plasmodium parasites. These advances are paving the way for large-scale, high-resolution monitoring of genetic variation in malaria parasites. Furthermore, enzymes responsible for the metabolism of antimalarial drugs have been shown to vary in the sequence of the human genes coding for them resulting in varying metabolic efficiency and possible failure of the drug to function accordingly. Apart from the impact of known human genetic polymorphisms related to protection against malaria, novel human gene polymorphisms are as well a major focus of this Project as they may reveal molecular processes that are critical for protective immunity, and will help us to understand the factors that could cause control measures to succeed or fail. Therefore, the goal of this project is to investigate important neglected aspects of malaria immunogenomics at four sites in Mali, representing three major eco-zones that span the sub-Saharan Sahel region. Study sites are already well characterized with respect to parasite populations, seasonal P. falciparum transmission, and malaria epidemiology. This project, which builds on extensive preliminary studies in Mali, includes three specific aims: (1) investigate the genetic diversity of P. falciparum in Malian communities living in different malaria endemic areas, and its relation with disease outcome; (ii) quantify P. falciparum gametocytes using molecular approaches in different epidemiological settings of malaria transmission in Mali, and (iii) assess the host genetic variability and antimalarial molecular markers of resistance in Malian populations living in areas of distinct transmission patterns and compare to parasite genetic diversity.

ICEMR的这一项目侧重于疟疾寄生虫和人类的遗传变异 及其对疟疾传播和疟疾控制措施效力的影响 在西非马里的四个地点。基因组研究的最新进展提供了前所未有的 有机会解决几十年来免疫学研究未能解决的问题，如 人们如何自然地清除血液中的疟疾寄生虫， 严重的疟疾通过研究人类和寄生虫的自然遗传变异如何影响 疟疾易感性，以及控制疟疾的努力，我们可以建立一个宿主/寄生虫目录， 对保护性免疫至关重要的分子。最近，恶性疟原虫已经发展成 对最有效的抗疟药物青蒿素的耐药性，以及 基因组是控制疟疾的主要障碍。现在，下一代测序方法 随着统计学和信息学的进步，我们研究遗传变异的能力已经改变， 疟原虫。这些进步为大规模、高分辨率铺平了道路 监测疟原虫的遗传变异。此外，负责 抗疟疾药物的代谢已被证明在人类基因序列中是不同的 编码它们导致不同的代谢效率和药物功能的可能失败 相应地除了已知的人类遗传多态性的影响， 针对疟疾，新的人类基因多态性也是该项目的主要重点，因为它们 可能揭示对保护性免疫至关重要的分子过程，并将帮助我们 了解可能导致控制措施成功或失败的因素。因此，这一目标 该项目是在马里的四个地点调查疟疾免疫基因组学中被忽视的重要方面， 代表了横跨撒哈拉以南萨赫勒地区的三个主要生态区。研究地点已经很好 特征在于寄生虫种群、季节性恶性疟原虫传播和疟疾 流行病学该项目以马里广泛的初步研究为基础，包括三个具体目标： (1)调查生活在不同疟疾地区的马里社区恶性疟原虫的遗传多样性 流行区，及其与疾病结果的关系;（ii）定量恶性疟原虫配子体使用 在马里疟疾传播的不同流行病学背景下的分子方法，和（iii） 评估马里人的宿主遗传变异性和抗疟耐药分子标记 生活在不同传播模式地区的人群，并与寄生虫遗传多样性进行比较。