Research Projects

Lack of an effective vaccine is one of the primary impediments to malaria eradication programs worldwide. Given the ability of the malaria parasite Plasmodium falciparum to develop drug resistance rapidly, an effective vaccine is essential to tackle the spread of this debilitating disease. One of the major challenges to designing a vaccine is the parasite’s remarkable ability to evade the host immune response through antigenic variation. During blood-stage infection, P. falciparum varies the expression of a specific surface antigen called PfEMP1 (P. falciparum Erythrocyte Membrane Protein 1) which mediates cytoadherence of parasitized erythrocytes to the host endothelium and hence ensures persistent infection. While the abundance of PfEMP1 on the parasitized erythrocyte surface makes it an attractive target for antibody-mediated host immunity, the parasite genome contains ~60 copies of var genes that encode for PfEMP1 - through a phenomenon called mutually exclusive expression, the parasite changes the surface-expressed PfEMP1 antigen and consequently evades immune clearance. Over the past 15 years, concerted efforts from researchers across the globe have identified key regulators of mutually exclusive var expression. However, less is known about the switching rates of individual var genes and the processes that regulate it. In the proposed study, we will use a multipronged approach that combines machine learning-based models and state-of-the-art single cell experimental approaches to derive var switching rates and validate them. We will also advance the field of var biology by exploring the influence of selected epigenetic factors on var switching and hierarchical patterns, and anticipate gaining important mechanistic insights into these processes.