Brian Tarimo (PhD student, NMAIST, Tanzania)
Plasmodium is a large genus of parasitic protozoa responsible for causing malaria, which are transmitted between human hosts by blood-feeding Anopheline mosquitoes. My current research interest focuses on malaria transmission biology, particularly on Anopheles mosquito’s ability to handle oxidative stress in relation to the Plasmodium parasite development in its midgut. The malaria parasite, Plasmodium, must undergo several development stages (sporogonic cycle) in an Anopheles mosquito for it to be infectious to a human host when the mosquito takes subsequent blood meals. Life in the mosquito is extremely challenging for Plasmodium and presents several bottlenecks in its development such that the parasite experiences a more significant reduction in its numbers than anywhere else in its life cycle. Factors contributing to this reduction are both human and mosquito derived. These factors cause oxidative stress in the surrounding cells, which could be harmful to both the developing parasite and midgut epithelial cells of the mosquito. The ultimate survival of both the parasite and mosquito depends on the innate ability to handle the oxidative stress.
My research background is in Bioinformatics; during my MSc degree I worked to develop a mathematical model for Glutathione (GSH) metabolism in Plasmodium falciparum during its erythrocytic stages. I am interested in understanding host-parasite interactions, both in the human and mosquito, which drive malaria transmission. A better understanding of the human-parasite-mosquito interactions that make Plasmodium transmissible to mosquitoes and humans could lead to development of novel interventions to break the cycle of transmission. I am also interested in utilizing my informatics skills in the analysis of data generated from high throughput techniques in acquiring such knowledge.
As a PhD student in the Dinglasan laboratory, I have been working with a protein of the Thioredoxin system (Trx) in Anopheles gambiae called Thioredoxin-1 (AgTrx-1). I focus on its involvement in redox regulation in the mosquito midgut epithelial cells. An Anopheles mosquito mounts an immune response when it ingests a Plasmodium-infected blood meal by producing excessive reactive oxygen species and reactive nitrogen species (ROS and RNS). This excessive ROS and RNS lead to oxidative stress and harms Plasmodium parasite and epithelial cells of the Anopheles midgut. Little is known about how Anopheles mosquitoes handle this oxidative stress in comparison to the extensive knowledge that exists of how the Plasmodium parasite handles this oxidative stress. Anopheles mosquitoes, like other dipterans, lack the enzyme glutathione reductase (GR), and therefore rely on the Trx system to deal with the oxidative stress. The main objective of my thesis research is to assess the transcript and protein expression levels of AgTrx-1 under varied oxidative stress conditions, first by trying to understand the basic molecular biology of how AgTrx-1 works in response to the stress. Then I will work to understand the global picture of transcriptomics and proteomics associated with different oxidative stress conditions in Anopheles gambaie midgut epithelial cells during P. falciparum ookinete invasion. Gaining understanding of the mosquito midgut epithelia’s response to oxidative stress will provide insight into the mosquito’s essential redox regulation repertoire. When understood, the mosquito redox system could unveil mechanisms for Plasmodium transmission blockade. Harnessing these mechanisms could ultimately lead to the prevention of human infections with this deadly parasite.