Analyses on membrane trafficking mechanism related to severe malaria

The majority of research and development aimed at malaria countermeasures focuses on drug development through screening, and research approaches that challenge the mechanism of disease onset from the perspective of the interaction between malaria parasites and the host are rarely taken. However, this is still largely ignored. The purpose of this study was to determine whether the protozoan proteins and host cell proteins responsible for the rosetting of infected red blood cells and their adhesion and binding (sequestration) with vascular endothelium, which are responsible for the aggravation of the pathology of malaria, are present in infected red blood cells. The aim is to elucidate the mechanism by which cells are transported by membrane traffic and presented to infected red blood cell membranes.
This year, the study analyzed the behavior of protozoan proteins identified through proteome analysis of Maurel’s fissure constituent proteins of malaria parasites in infected red blood cells.
(i) We organized the proteome analysis data obtained by mass analysis of Maurel’s fissure was organized, gene ontology analysis was performed and factors related to protein transport was narrowed down.
(ii) The study sorted into proteins that retain the PEXEL motif (RxLx(D/E/Q)), which is thought to be possessed by transport proteins, in their amino acid sequences and proteins that do not have the motif (non-PEXEL).
(iii) In order to verify whether the protozoan proteins narrowed down in (i) and (ii) are actually transported to the Maurel fissure, a plasmid expressing a fusion protein of GFP and the target protozoan protein was electroporated into the protozoan protein, introduced into the cells, and their behavior within red blood cells was analyzed.

Project details

Basic Science

Apr 2020 — Mar 2023

$157,068

Japan