Dr. Mackey studies essential DNA metabolizing genes in Tryoanosoma brucei. He hopes to identify differences in the pathways of the parasite that can be exploited to develop novel drug treatments. The parasite causes African sleeping sickness and affects approximately 30,000-50,000 people per year in sub-Saharan Africa where it is transmitted via the tsetse fly.
The goal of our research is to understand in mechanistic details how to therapeutically exploit divergent features in the DNA replication machinery of bloodstream form Trypanosoma brucei. This vector-borne parasite causes African trypanosomiasis, a fatal meningoencephalitic disease that is in great need of new therapies because the current ones are ineffective, highly toxic, and difficult to administer to patients. Targeting components of the DNA replication machinery presents an attractive strategy for the development of new antiparasitic drugs. The focus of my laboratory is to target theproliferating cell nuclear antigen homolog in T. brucei (TbPCNA, which is an essential DNA replication factor. PCNA homologs also functions in chromatin reorganization, DNA repair, and cell cycle regulation through a plethora of protein interaction it makes. Over 200 proteins interact with human PCNA (HsPCNA) through a conserved motif known as thePCNA interacting peptide motif (PIP-box), many of which are essential in eukaryotic cells. Our strategy is to identify and target TbPCNA interactions that are essential for parasite survival.