Malaria, caused by protozoa of the genus Plasmodium, is one of the main public health problems worldwide. The disease occurs in 109 countries and is endemic in tropical and subtropical regions of Africa, Southeast Asia and Latin America. Virtually, half the world's population (3.3 billion people) is exposed to malaria transmission. In 2013, 198 million cases and 584,000 deaths were reported, most of them in Africa (WHO, 2014). The emergence of drug resistance cases boosts the search for new molecular targets and the development of chemotherapeutic agents against the disease.The research project aims at (i) the elucidation of the three dimensional structure of the phosphatidylinositol-4-OH kinase (PI4K), an important enzyme in the metabolism of Plasmodium; (ii) the development of in vivo and in vitro assays for screening compounds as antimalarial candidate and (iii) the discovery and development of new bioactive compounds as drug candidates for malaria. To this end, integrated studies in structural molecular biology, enzyme kinetics, cell biology, parasitology and pharmacology will be employed. Phosphatidylinositol-4-OH kinase (PI4K), a ubiquitous eukaryotic enzyme, is responsible for phosphorylation of lipids and participates in the regulation of intracellular signaling and transport vesicles. The enzyme was recently described as essential in all cell cycle stages of the parasite. Furthermore, PI4K has significant differences related to the human homologous protein, thereby the enzyme is an attractive molecular target for the development of new antimalarials. The project will be developed in Laboratory of Medicinal and Computer Chemistry - LQMC, held at the Center for Innovation in Biodiversity and Drugs - CIBFar-CEPID in the São Carlos Institute of Physics, USP. The LQMC-CIBFar laboratories have complete infrastructure to accomplish all the steps proposed in this research project.
News published in Agência FAPESP Newsletter about the scholarship: