Research Projects

This proposal focuses on the "cullin-RING ubiquitin E3 ligases" of the human malaria pathogen P. falciparum, which threatens around 40% of the world population and causes about 200 million cases and half a million deaths annually. The complex parasite life cycle contributes to the poor understanding of malaria parasite biology. A systematic investigation of Plasmodium development and disease pathogenesis will enhance our understanding of parasite biology and reveal novel potential drug and vaccine targets. The ubiquitin proteasome system (UPS) is a fundamental pathway in eukaryotes and has been shown to be an attractive drug target for various diseases. Inhibition of Plasmodium UPS synergizes the potency of artemisinins, the main component of current antimalarials, in both artemisinin susceptible and resistant P. falciparum strains. Ubiquitin E3 ligases dictate substrate specificity and are present in a large number to cover the cellular proteome. The study will investigate the functions and regulation of Plasmodium culling-RING ubiquitin E3 ligases, potentially unraveling their mechanisms in parasite development and validating them as new targets for chemotherapeutic intervention of malaria. The proposed objectives will be achieved using a combination of genetic manipulation, standard cell biology, mass spectrometry, protein-protein interaction, and standard biochemical techniques. The PI's lab has proven expertise in all the techniques required to achieve these objectives.