Genomic Studies of the Impact of External Factors on Parasite Development and Disease Outcome

尽管近几十年来取得了重大进展，但寄生虫病仍然是造成艾滋病的主要原因之一。 死亡率和发病率。仅疟疾寄生虫和蠕虫就造成了全球一半以上的疟疾病例。 每年有10亿例临床感染，世界人口的一半处于危险之中。在这里，我们提出实验 旨在利用最先进的基因组技术来解决外部因素对寄生虫的影响 发展和疾病的结果，重点是共同感染和宿主性别的影响。虽然共同- 感染多种寄生虫是常见的，多寄生虫对疾病传播的后果 结果仍然知之甚少。我们将使用单细胞基因表达分析来研究 药物治疗以及与多种疟原虫寄生虫的合并感染影响寄生虫的传播 从宿主到蚊子，使用非人类灵长类动物模型。利用基因组学和 转录组学方法，我们将描述正在进行的埃及血吸虫感染的影响， 宿主对儿童疟疾感染的免疫反应，调查是否有免疫调节作用 血吸虫病是持久的，并确定它是否影响感染疟疾的基因型 寄生虫最后，我们将使用动物模型来研究宿主性别和感染部位对 丝虫线虫的发展及其对宿主雄性中不同药物效力的推定后果 和女性。这些多学科的研究代表了定量表征的第一步， 共感染对寄生虫感染结果的作用，以及寄生虫感染中宿主性别偏见的调查 感染研究。这两个主题尚未得到充分研究，但却影响着全球数百万人。的 这些发现的意义可能是广泛的，包括研究寄生虫感染的新方法 以及人类和动物模型中的合并感染，以及对免疫接种和 高度优先寄生虫病的治疗方法。

Despite significant progress in recent decades, parasitic diseases remain among the principal causes of mortality and morbidity worldwide. Malaria parasites and helminths alone are responsible for more than half a billion clinical infections every year, with half of the world’s population at risk. Here, we propose experiments aimed at using state-of-the-art genomic technologies to address the impact of external factors on parasite development and disease outcome, with an emphasis on the influence of co-infection and host sex. While co- infections with multiple parasites are common, the consequences of poly-parasitism on disease transmission and outcomes remain poorly understood. We will use single-cell gene expression analyses to examine how drug treatment, as well as co-infections with multiple Plasmodium parasites, influence parasite transmission from hosts to mosquitoes, using a non-human primate model. Using a combination of genomics and transcriptomics methods, we will characterize the effect of ongoing Schistosoma haematobium infection on the host immune response to malaria infection in children, investigate if the immunomodulation exerted by schistosomiasis is long-lasting, and determine whether it impacts the genotype of the infecting malaria parasites. Finally, we will use an animal model to investigate the impact of host sex and site of infection on the development of filarial nematodes, and its putative consequences on differential drug efficacy in host males and females. These multi-disciplinary studies represent an initial step in the quantitative characterization of the role of co-infection on the outcome of parasitic infections, and in the investigation of host sex biases in parasitic infection studies. These two topics are critically understudied and yet impact millions of people worldwide. The implications of these findings could be wide-ranging, and include novel approaches to study parasitic infection and co-infections in human and animal models, as well as public health insights into immunization and treatment approaches in high-priority parasitic diseases.