Elucidation of lipid molecule recruitment mechanism in intrahepatic Plasmodium

Plasmodium, which is the cause of malaria, invades the human body along with the blood-sucking of mosquitoes. After multiplying in the liver, the protozoa migrate to blood vessels and infect red blood cells. The ecology of intrahepatic malaria parasites is still unclear compared to the erythrocytic stage, and the current situation is that there are few effective drugs. At the hepatocyte stage, the parasite forms a parasitic vesicle (PVM) and multiplies more than 10,000 times in it. Protozoa require a large amount of lipid molecules as a cell membrane component in a short period of time in order to multiply rapidly, but it is considered difficult to supply the required amount of lipid molecules with the lipid synthesis system of protozoa alone. Therefore, if there is a system for supplying lipid molecules from the host cell to the protozoan, the protozoan can rapidly obtain the necessary amount of lipid molecules. Lipid droplets are thought to be one source of these lipid molecules. Lipid droplets are not mere lipid reservoirs, but structures that supply lipids by forming complexes with various organelles by several proteins. Intrahepatic-stage malaria parasites have been observed to attract host organelles around the PVM, suggesting that parasites obtain lipid molecules necessary for proliferation using the lipid supply system of lipid droplets. is high. Therefore, it is necessary to clarify the dynamics of lipid molecules between the parasite and the lipid droplet-organelle complex in order to clarify the molecular basis for the rapid proliferation of intrahepatic malaria parasites. Therefore, the focus will be on the lipid droplet-organelle complex, which is thought to be the source of lipid molecules, and analyze the effects of malformation of the complex on protozoan proliferation. This reveals which organelle-lipid droplet complex supplies lipid molecules to the parasite. In addition, by analyzing the composition of the supplied lipid molecules, the project will investigate what kind of lipid molecule group supports the proliferation of protozoa.

Project details

Basic Science

Apr 2021 — Mar 2024

$31,209

Japan