In areas of high malaria endemicity, repeated parasite exposure results in individuals developing naturally acquired immunity (NAI). To understand NAI and to help prioritize antigens for vaccine development, our lab is creating a novel bead-based assay in which parasite antigens are captured directly onto microsphere bead sets and then exposed to patient sera to characterize antigen-antibody binding. This is expected to facilitate surveillance of malaria in low-transmission zones.
A combination of CRISPR/Cas9 mediated gene knockout with a chemical rescue strategy has helped dissect the essentiality of an apicoplast-targeted topoisomerase. This gene-editing system has also allowed us to confirm point mutations associated with antimalarial resistance against other targets and can be universally applied to other proteins to further dissect Plasmodium resistance mechanisms. Additionally, our lab utilizes a catalytically inactive Cas9 enzyme, termed dCas9, to investigate target validity within the parasite.
Proteomics for drugs
Matching a bioactive compound with its target can greatly accelerate drug discovery and lead optimization. In addition to genetic approaches, we are currently developing a label-free proteomics workflow to identify novel protein-inhibitor interactions in complex biological mixtures. This is expected to reveal targets without requiring derivatization or immobilization of a given small molecule inhibitor. Additionally, genetic technologies cannot simultaneously report on multiple protein-inhibitor interactions.
Manuscripts in preparation.