Last Updated: 18/11/2024
Elucidation of molecular mechanism to determine parasitic commitment of malaria parasite
Objectives
The aim of this study is to investigate the molecular mechanisms that regulate the transition of Plasmodium sporozoites from the mosquito midgut to salivary glands and subsequently to hepatocyte invasion. The study aims to provide a deeper understanding of the molecular pathways and regulatory mechanisms that underpin the lifecycle transitions of Plasmodium sporozoites, with potential implications for malaria intervention strategies.
[Localization of 6-cys protein P-41 required for hepatocyte recognition] Studies up to last year revealed that P41 is an essential molecule for recognizing hepatocytes and converting from the motor stage to the parasitic stage. rice field. This year, using the double-CRISPR Cas9 system established last year, an epitope tag was inserted at the N-terminus of the P41 protein, and localization was successfully detected. As a result, it was clarified that P41 is localized to the microname of sporozoite as well as P36p. From this result, the results of previous knockout studies that P36p and P41 play similar roles were confirmed in terms of the intracellular behavior of proteins. [Analysis of transcription factor AP2-Sp3] The researchers have analyzed AP2-Sp and AP2-Sp2 as molecules that control transcription during the sporozoite phase. AP2-Sp is expressed from the early stage of sporozoite formation in the midgut of mosquitoes and is responsible for transcriptional regulation of the entire sporozoite stage. On the other hand, AP2-Sp2 is expressed in the midgut of mosquitoes and is responsible for the regulation of genes required for sporozoite formation. However, these alone cannot explain the change in properties from midgut sporozoite to salivary gland sporozoite. Therefore, the team identified AP2-Sp3 from the results of expression profile analysis of AP2 family proteins of unknown function. Furthermore, AP2-Sp3 was fused with a GFP tag, and the target gene was comprehensively identified by ChIP-sequence using an anti-GFP antibody. As a result, the molecules required for hepatocyte invasion of sporozoite were mainly identified. We also identified proteins involved in the transfer of mosquitoes from the midgut to the salivary glands. From this result, it was clarified that AP2-Sp3 regulates the function after AP2-Sp2, that is, the gene cluster after the salivary gland of sporozoite and during the hepatocyte invasion stage.
Apr 2018 — Mar 2021
$28,534
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