Plasmodium parasite motility: identification of new candidates for drug targeting and validation of vaccine candidates

Abstract

Motility is essential for malaria parasites in order to achieve vector colonization, natural transmission, and vertebrate host pathogenesis. Forward locomotion and host cell invasion in Plasmodium motile stages are dependent on the same actin-myosin based motor machinery. In this proposal, we aim to improve the current understanding of ookinete and sporozoite motility in order to design targeted intervention strategies and eventually interfere with malaria transmission. We propose to identify and validate new target molecules for chemotherapeutic approaches by addressing the molecular mechanisms of small heat shock proteins that regulate Plasmodium motility. Additionally, we want to evaluate efficacy and capacity to elicit long-term sterile protection of a leading P. vivax malaria vaccine candidate. Within the current proposal we aim to generate transgenic malaria parasites and develop a preclinical murine infection model to systematically test different P. vivax vaccine immunization strategies. The ultimate goal of this project is to establish the rodent Plasmodium life cycle and experimental genetics in Brazil, which is a crucial model for the development and testing of novel evidence-based tools for malaria control. (AU)