Graduate student works to shut down one pathway, and make all the difference
Once the malaria-causing parasite Plasmodium falciparum enters the human body through an infected mosquito’s bite, it takes less than 48 hours to cause a full-on infection, devouring red blood cells and in serious cases, ending in coma or death. Malaria is the third human killer across the globe and is particularly rampant in sub-Saharan Africa. Scientists have identified a metabolic pathway, or sequence of biochemical reactions, called the methylerythritol phosphate pathway (MEP) that the parasite uses to make isoprenoids—molecules important for life in all asexual stages of the parasite.
Biochemistry graduate student Jessica Bowman is working with Maria Belen Cassera, assistant professor of biochemistry and Fralin affiliated faculty member, to determine how the pathway works, and ultimately, develop drugs to work against it. Working with other members of Cassera’s lab, including research scientists Fernando Merino and Isabel Da Fonseca, Bowman clones and expresses pathway enzymes, observes the reactions under microscope, and then screens and develops drugs to inhibit the reactions. Flow cytometry, IC-50 assays, mass spectrometry, and other scientific techniques are used to isolate and study targets.
“Now that we know the pathway is there, we are trying to shut it down,” Bowman explained. “If we block the enzymes involved in the chemical reaction, we can stop the reaction from taking place.”
Specifically, Bowman investigates the reactions that occur in the apicoplast, a non-photosynthetic “plastid” in all strains of the Plasmodium family determined crucial to the parasite’s survival.
But stopping the pathway is easier said than done. P. falciparum and its sister malaria-causing parasites, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariaeare known for drug resistance. The parasites have two stages—asexual and sexual—which makes it difficult to develop one drug that can target both stages.
On the bright side, the metabolic pathway does not appear to be used by human cells, and therefore, drugs developed to inhibit it would likely have few side effects for humans. Finding clues that will lead toward development of the perfect anti-malarial drug is in line with Bowman’s overarching goals of continuing to work in vaccine and drug development long term.