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.
Q &A : Meet Jess
Biochemistry (2nd year)
Dr. Maria Belen Cassera
Biochemistry and Molecular Biology, B.S., Liberty University
Why do you want to be a scientist?
I really love studying the most basic components of ‘life’ and how everything works together to function correctly. I also want to affect the world, and I know that all science will benefit society in some way, shape, or form. Lastly, I like to be challenged and it is so cool when scientific challenges are overcome.
When did you know?
I had a vague idea that I wanted to pursue the sciences in my senior year of high school when I took an advanced biology class. I knew I wanted to make it my career when I did an internship at MedImmune biotech company in Gaithersburg, Maryland, during my junior year of college.
What attracted you to your particular field of science?
Biochemistry is the best of both biology and chemistry. I really like how it fuses the two fields and how intricate the field truly is. Also, working with malaria and drug discovery was attractive because of the great need of new anti-malarials.
Your best Eureka! Moment (when something cool happened in your research):
Taking a project from its infancy and seeing even the smallest promising results is so rewarding. I am a very visual person so seeing a fluorescent parasite under special UV microscopes or seeing the effect of a drug on an enzyme or on the parasite itself is so cool. Even the little advances in our research amount to “Eureka Moments” because we know how much work went into making those advances. (Great show by the way!)
What are your ultimate career goals?
I know I would like to be involved in some kind of vaccine/drug development research (or development) long term. At the moment, I am leaning towards industry but also like a lot of the government positions in my field.
If you were a component of a human cell, what would you be and why?
Nucleus hands down! Because your DNA is located there and then I could do cool things like mitosis and meiosisJ.
Which quality of the following do you feel is the most important for a scientist to possess—open-mindedness, precision, time management skills, optimism, cynicism, integrity, a good sense of humor?
Wow, this is a big question. I would say that passion is the best quality for a scientist to possess because if you are passionate about your research, you will go to any length to progress it. This will lead to being open-minded, precise, optimistic/cynical, and you will learn to have a good sense of humor. Being passionate about your work will usually lead to being a person of integrity, having good time management skills, and being joyful about your work.