Research: The Effect of Host Aquaglyceroporins on the Intrahepatic Proliferation of Plasmodium Sporozoites
Awards: Westlake Science Fair 2021 Participant
Mentor: Dr. Sebastian Bol
Abstract:
Malaria is an infectious disease that is caused by the Plasmodium parasite and kills approximately half a million people per year. When Plasmodium first invades its host, it goes to the liver to replicate and uses the host’s aquaporins (membrane proteins that transport water and other small solutes) to benefit its development (Posfai, 2018). AQP3, AQP7 and AQP9 transport water, glycerol, and urea in mammalian cells, but only AQP7 or AQP9 are usually expressed in the liver. However, AQP3 is primarily used by the parasite for its development, and as such the hypothesis of this research is that AQP3 transports glycerol and urea at a significantly faster rate than AQP7 and AQP9. The minimum fatal concentration of urea deadly to the parasites was determined, as well as the optimal glycerol concentration beneficial to parasite proliferation. HC-04 hepatocyte cell lines were cultured and infected with Plasmodium falciparum sporozoites. Two of the three AQPs of interest were silenced through CRISPR, while one AQP was left expressed in order to assess the rate at which urea was exported outside the cell and glycerol was imported inside the cell. Results showed that the rate of glycerol transport for AQP3 is significantly higher than the rate of glycerol transport for AQP7 (p-value < 0.001). The rate of glycerol transport for AQP3 is also significantly higher than the rate of glycerol transport for AQP9 (p-value is <0.001). However, urea transport of AQP3 is significantly slower than AQP7’s and AQP9’s (critical t-value was negative in both cases). Results support the idea that Plasmodium uses glycerol to make phospholipids needed for plasma membranes as it replicates and develops in the liver. This discovery will assist in the development of future therapeutic treatments that focus on inhibition of AQP3’s glycerol transport.
About this Scientist:
Nirel Ayertey is a junior who is currently pursuing her IB Diploma at Yonkers High School. After many failed attempts at finding someone to help her with her research, Nirel has found a mentor in San Antonio, Texas, where she will be spending the majority of her summer continuing her research. Nirel’s future plans include getting an M.D. and becoming a pathologist, in order to pursue her dream of working in a laboratory to help study and diagnose diseases.
Hi Nirel! I am super interested to learn more about the liver stage of infection -- it certainly seems like an innovative pathway through which to explore further malaria treatments