Probing Pathogen and Host Proteins in Plasmodium Infection

Malaria is responsible for hundreds of thousands of deaths annually and is a challenge to treat due to growing resistance to medications by the disease-causing parasite, Plasmodium. Therefore, it is necessary to expand the understanding of the Plasmodium parasite life cycle and its biochemistry to better treat and prevent this disease. This research explores parasite and host protein chemistry and biology to elucidate mechanisms of parasite survival and host response. A small molecule inhibitor was recently found to have activity against the Plasmodium falciparum kinase 9 (PfPK9), so a structure-activity relationship campaign was used to optimize small molecule inhibitors to this orphan kinase. Inhibition of this kinase with no known human homologues reduces parasite load in human cell infection and provides a promising route of action for future antimalarial chemotherapeutics. Additionally, the Plasmodium binding partners of PfPK9 were studied to better understand its essential role in the parasite life cycle. Finally, microscopy studies were used to explore a new and exciting area of innate immunology – that of human guanylate-binding protein (hGBP) recognition of invading parasites.