The molecular basis of Hepatocystis, the closest relative of malaria (Plasmodium) parasites

肝囊原虫是哺乳动物疟原虫的近亲，感染一系列灵长类动物和蝙蝠。在感染疟原虫寄生虫时，红细胞内无性血液阶段的复制是疟疾疾病的唯一原因。这一致病性生命周期步骤存在于疟原虫属的物种中，但在所有其他哺乳动物血孢子虫寄生虫中缺失。一个全面的寄生虫学和分子生物学调查密切相关的疟疾寄生虫，如肝囊原虫，有助于我们了解寄生虫/宿主共同进化的重要媒介传播的传染病。目前对肝囊原虫的认识与疟原虫研究的早期相当，这些寄生虫的基本特征存在严重的知识空白。对肝囊原虫的研究在很大程度上被忽视了，尽管这种寄生虫属具有几个重要的特征，对它们的研究可以更好地了解整个疟疾寄生虫家族。此外，肝囊肿寄生虫与其蝙蝠宿主共同进化，蝙蝠宿主以其非凡的长寿，先天免疫防御和物种多样性而闻名，因此呈现出独特的研究系统。在我以前的研究基础上，我建议通过研究肝囊原虫的肝脏和血液阶段转录组的基因组，哺乳动物疟原虫物种的最近亲属，与已发表的血孢子虫数据集的比较方法，来了解红细胞裂殖体的进化。此外，我将研究血液阶段的感染和潜在的相应的健康影响，在乌干达的自然蝙蝠宿主肝囊原虫寄生虫系统。这些研究结果也将允许的结论，特定的哺乳动物疟原虫寄生虫，宿主适应性和致病性的生活史特征的演变。

Hepatocystis parasites are the closest relatives of mammalian Plasmodium species and infect a range of primates and bats. In infections with Plasmodium parasites intra-erythrocytic replication of asexual blood stages is the exclusive cause of malaria disease. This pathogenic life cycle step is present in species of the genus Plasmodium, but missing in all other mammalian haemosporidian parasites. A comprehensive parasitological and molecular investigation of a closely related malarial parasite, such as Hepatocystis, contributes to our understanding of parasite/host co-evolution of the important vector-borne infectious disease. The current knowledge of Hepatocystis parasites is comparable to the early days of Plasmodium research, with critical knowledge gaps of basic characteristics of these parasites. Research on Hepatocystis has been largely neglected, although this parasite genus is characterized by several important features and their investigation could lead to a better understanding of the entire family of malaria parasites. Further, Hepatocystis parasites co-evolved with their bat hosts, which are known for their exceptional longevity, innate immune defense, and species diversity and therefore present a unique study system. Building on my previous research, I propose to work to an understanding of the evolution of erythrocytic merogony by studying the genome in combination with the liver and blood stage transcriptomes of Hepatocystis, the closest relative of mammalian Plasmodium species, in a comparative approach with the published haemosporidian datasets. In addition, I will study the blood stage infection and potential corresponding health effects in the Hepatocystis parasite system in natural bat hosts in Uganda. These findings will also allow conclusions about the evolution of the life history traits specific to mammalian Plasmodium parasites, host adaptation and pathogenicity.