Grant: Operating Grant

Malaria is one of the world's most common infectious diseases, with approximately 274 million cases each year and 1 million deaths, and thus represents one of the most devastating global public health problems. The lack of an effective vaccine, the emergence of resistance to first-line drugs like chloroquine and antifolates and recent reports of clinical cases of reduced susceptibility to artemisinine in Cambodia, combined with the small number of suitable new drugs against the malaria parasite demonstrate the urgent need for the development and implementation of novel intervention strategies in the form of drugs, vector control measures and an effective vaccine. Indeed, it is expected that if the trend in malaria prevalence stays on its current upwards course, the death rate could double in the next twenty years. Invasion of a red blood cell by Plasmodium falciparum parasites is an essential step in the malaria lifecycle and host response to parasite antigens are an important component of human malarial immunity. Consequently, the molecular players involved in erythrocyte invasion are key targets for both therapeutic and vaccine-based strategies to block parasite development. Several of these invasion proteins are stored in the apical complex of the parasite, a structure containing secretory organelles called dense granules, micronemes and rhoptries, and are released at different times during invasion. Because of its essential role, interfering with the generation of the apical complex represents a very attractive target for the design of a new kind of antimalarial. Our studies will focus on trying to understand how the parasite directs proteins to the different structures of the apical complex. Understanding this complex process will likely provide a wealth of new targets for the development of strategies to block apical complex generation and preventing malaria pathogenesis.