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

肝囊虫是哺乳动物疟原虫的近亲，感染多种灵长类动物和蝙蝠。在疟原虫感染中，红细胞内无性血期复制是疟疾的唯一病因。这一致病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都不存在。对一种密切相关的疟疾寄生虫（如肝囊虫）进行全面的寄生虫学和分子研究，有助于我们了解这种重要的媒介传播传染病的寄生虫/宿主共同进化。目前对肝囊虫寄生虫的认识与疟原虫研究的早期相当，对这些寄生虫的基本特征存在严重的认识差距。肝囊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，对它们的调查可以更好地了解整个疟疾寄生虫家族。此外，肝囊虫寄生虫与它们的蝙蝠宿主共同进化，它们以其超常的寿命、先天免疫防御和物种多样性而闻名，因此提供了一个独特的研究系统。在我之前研究的基础上，我建议通过研究肝囊虫（哺乳动物疟原虫的近亲）的基因组，结合肝囊虫的肝脏和血液阶段转录组，与已发表的血孢子虫数据集进行比较，来了解红细胞分型的进化。此外，我将研究乌干达天然蝙蝠宿主的肝囊虫寄生虫系统的血期感染及其潜在的健康影响。这些发现还将有助于对哺乳动物疟原虫特有的生活史特征的进化、宿主适应和致病性得出结论。

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.