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

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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.