Julian Rosenberg

Malaria is a disease that infects approximately 229 million people per year and is responsible for about half a million deaths per year. Malaria is transmitted through the bite of a mosquito that carries a parasite called Plasmodium falciparum, which replicates within the body causing flu-like symptoms. The danger of malaria comes from its ability to remain in the body for up to a year. Plasmodium falciparum evades the immune system through a constant switching between var genes that encode a protein called PfEMP1. Parasites switch genes so that only one gene is expressed at a time, a process known as antigenic variation. Without antigenic variation, malaria cannot remain in the body for long periods of time. It is proposed that an RNA degradation pathway called nonsense-mediated decay is involved in triggering var gene switching. The nonsense-mediated decay pathway is composed of many known genes, one of them being called SMG6L. In my project, I aim to conclude whether SMG6L affects the antigenic variation and the nonsense-mediated-decay pathway. Through the use of the genome-editing tool CRISPR-Cas9, SMG6L will be knocked out to evaluate how the elimination of nonsense-mediated decay influences the parasites’ ability to switch var gene expression. Initial PCR analysis points to an effective knockout of SMG6L. Final results suggest that the elimination of SMG6L does not affect var gene switching. However, more work is needed to verify this because the significant expression levels of a different gene, var45, may signify that var45 possesses unique properties that limit the parasite’s ability to switch to var2csa. By researching more into how antigenic variation is disrupted, the scientific community can learn how to dismantle malaria’s greatest weapon: the ability to avoid the immune system for prolonged periods of time.

Link to Research Paper

Awards and Competitions

Terra NYC Stem Fair Finalist, 2023