Molecular dissection of the dormancy and pathogenicity in malaria: a simian and zoonotic malaria toolkit

 The protozoan parasite Plasmodium is the etiological agent of malaria that is transmitted by the Anopheles mosquito to human (or simian). The Plasmodium liver-stage parasite represents the first intracellular infectious step in human following a mosquito bite, and this asymptomatic stage forms several thousands of merozoites with tremendous multinuclear hyper-proliferation. Some Plasmodium species generate a dormant uninucleate parasite during liver-stage development termed the hypnozoite which persists for months or even years following an infection. The developmental decision-making that controls dormancy (or promote proliferation) in Plasmodium liver-stage is made before nuclear segregation. Hence, liver-stage development may play an important role in host adaptation through the production of first generation of merozoite. However, the detailed molecular mechanism(s) that regulates proliferation is poorly understood.
Our group is interested in unraveling the mechanism(s) of how the Plasmodium liver-stage parasite controls proliferation and also how the parasite survives inside the hepatocyte, especially during the dormant hypnozoite stage. We develop and use cutting-edge molecular approaches to understand malaria parasite biology, the host adaptation, and the mechanisms of host immunity and parasite pathogenesis. We employ several parasite models, such as simian malaria parasites which is recognized as a zoonotic malaria parasite in Asian countries. To reveal the detail of molecular mechanism of liver-stage development and host adaptation, we have succeeded to generate transgenic parasites by using these malaria parasites. Furthermore, we have been approaching to setting up human malaria parasite infection into Bolivian Squirrel Monkey. The progress of these projects and the future direction of our collaboration will be discussed.