Plasmodium's Crossroads: Deciphering the Molecular Pathway That Leads to Malaria Transmission

Abstract

Plasmodium falciparum is the causative agent of the most severe form of malaria. Transmission from humans to mosquito vectors is an essential step in this eukaryotic parasite‘s life cycle and in the spread of malaria disease, which killed nearly 600,000 people in 2013. I investigated the developmental switch parasites make to the transmission stage or gametocyte, with the goal of identifying molecular mechanisms and environmental triggers of gametocyte formation. In Chapter 2 of this dissertation, I discuss the completion of a genetic mutagenesis screen leading to the discovery of a putative E3 ubiquitin ligase enzyme which is likely a negative regulator of gametocyte formation. Chapter 3 presents findings on population-based regulation of gametocyte production and on parasite-derived microvesicles that transfer between cells and stimulate gametocyte production. In Chapter 4, I and coauthors present a protocol for measuring parasite growth and gametocyte production in response to drugs or other treatments.