Interdisciplinary Initiatives Program Round 7 - 2014

Ellen Yeh, Biochemistry, Pathology
Josh Elias, Chemical & Systems Biology

Malaria caused by Plasmodium spp parasites has an enormous global disease burden. New anti-malarials with novel drug mechanisms are desperately needed in the face of existing or emerging drug resistance to all available therapies. The apicoplast is a plastid organelle unique to Plasmodium spp (and other pathogenic parasites) and a key target for development of new anti-malarials. Despite intense focus on apicoplast biology and its therapeutic potential for nearly 20 years, to date, the majority of the apicoplast proteome has not been experimentally validated. Given the central role of the apicoplast in Plasmodium biology, the plastid proteome will be a rich source for novel biology and therapeutic drug targets. Proteomic analysis of the apicoplast would fill a major gap in our understanding toward fulfilling the promise of the apicoplast as a therapeutic target. The Yeh and Elias lab propose an innovative approach that combines advances in apicoplast biology and proteomics to address this significant and challenging problem. Using chemically-rescued “apicoplast(-)” parasites and a proteomic enrichment strategy, we propose to carry out the first experimental identification of the apicoplast proteome and globally map sequence determinants that direct organelle targeting.