Research Projects

Malaria remains a major parasitic disease in the tropical and sub-tropical countries that resulted in ~229 million cases and around 409,000 deaths globally in the year 2019 (WHO report 2019). Currently, there is no efficient vaccine and the rapid spread of drug resistant parasite strains, even to the front-line treatment using artemisinin combinations. Throughout the lifecycle, Plasmodium parasites remodel their host cells in numerous ways, including altering the host cell membrane and inducing the formation of various membranous compartments e.g. TVN , maurer’s Cleft. During this remodeling of the host cells, several proteins of parasite origin interacts with lipids in host cell in Plasmodium falciparum, and play different important roles in the life cycle of parasite. However not much is been known in case of Plasmodium vivax due to lack of continuous culture. Several Plasmodium vivax proteins are been reported to be present in cytoplasm of host cells i.e. infected reticulocytes , along with in parasitophorous vacuolar membrane, caveola–vesicle complex (CVC) and on the membrane of the parasitized reticulocyte of Plasmodium vivax. Whether they have role in development of these structures or they get trafficked utilizing these structures is not known. However, these observations points towards possible role of P.vivax proteins in lipid remodeling of the host. Lack of information regarding these P.vivax proteins, playing important role in host cell remodeling, needs to be addressed for development of effective therapeutic targets. One of such proteins are Plasmodium vivax tryptophan rich antigens (PvTRAgs), which belongs to pv-fam-a family of P. vivax. The number of tryptophan-rich proteins encoded by the P. vivax genome is much higher than that of P. falciparum. In the latter case, some of these proteins have been shown to play important role in red-cell invasion and thus are proposed as potential vaccine candidates against P. falciparum malaria. The stage-specific expression of these P. vivax tryptophan-rich protein genes is indicative of their different roles in the parasite's life cycle. Apart from 10 erythrocyte binding PvTRAgs, the biological significance of non–erythrocyte-binding PvTRAgs remains unknown, except that they are highly immunogenic in humans with limited genetic variation. Whether, the non-binder PvTRAgs are playing an important role in host remodeling and parasite growth, requires further investigation. In this proposal we suggest to identify the Lipid protein interactions and novel pathways involved in remodeling of both host and parasite in P. vivax. A multidisciplinary approach that combined with bioinformatics, molecular biology, lipid binding assay and Plasmodium vivax in-vitro culture will unravel the targets, substrates and regulators of these important pathways, which will be critical towards understanding of the mechanisms via which these lipid protein interactions regulate parasite division and development.