Mali ICEMR Project 2: Immunogenomics Epidemiology of Malaria in Mali

ICEMR的这个项目关注的是疟疾寄生虫和人类的遗传变异 宿主及其对疟疾传播的影响和疟疾控制措施的有效性 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 解决几十年免疫学研究未能解决的问题的机会，如 人们是如何自然地从血液中清除疟疾寄生虫的，或者为什么有些人会 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 疟疾易感性和控制疟疾的努力，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 对最有效的抗疟疾药物青蒿素的耐药性及其继续进化 基因组是疟疾控制的主要障碍。现在，下一代测序方法结合了 随着统计学和信息学的进步，改变了我们研究遗传变异的能力 疟原虫寄生虫。这些进展正在为大规模、高分辨率的 监测疟疾寄生虫的遗传变异。此外，负责代谢的酶 抗疟疾药物的新陈代谢已被证明在人类基因序列中有所不同 对它们进行编码会导致不同的新陈代谢效率，并可能导致药物失效 相应地。除了与保护有关的已知人类遗传多态的影响外 针对疟疾，新的人类基因多态也是该项目的主要焦点，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败的因素。因此，这一目标是 该项目是在马里的四个地点调查疟疾免疫基因组学被忽视的重要方面， 代表撒哈拉以南萨赫勒地区的三个主要生态区。研究地点已经很好了 以寄生虫种群、季节性恶性疟原虫传播和疟疾为特征 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)调查不同疟疾病区马里社区恶性疟原虫的遗传多样性 流行区及其与疾病转归的关系；(Ii)利用 在马里疟疾传播的不同流行病学背景下的分子方法，以及(3) 评估马里宿主的遗传变异性和抗疟疾分子标记 生活在不同传播模式地区的种群，并与寄生虫的遗传多样性进行比较。

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.