The Johns Hopkins Malaria Research Institute includes a group of investigators whose work focuses on the cellular and molecular events that enable the malaria parasite to live and replicate in its mosquito and mammalian hosts.
In-house insectary facilities enable us to complete the lifecycle in the laboratory and thus study the transmission stages, both to and from the mosquito, as well as the erythrocytic stages that give rise to clinical disease. Below is a synopsis of the parasitology work at the Johns Hopkins Malaria Research Institute.
Dr. Photini Sinnis studies the initiation of malaria infection in the mammalian host with the inoculation of sporozoites by mosquitoes. She is interested in how sporozoites exit the inoculation site and the cellular and molecular interactions that enable sporozoites to reach the liver and enter hepatocytes. Once in the liver, sporozoites must cross from the circulation into the liver parenchyma.
Dr. Marcelo Jacobs-Lorena studies the interactions between sporozoites and the Kupffer cells that line the hepatic sinusoids. He has identified receptors on the Kupffer cell that are critical for sporozoite passage into the liver. After entry into hepatocytes, sporozoites develop into exoerythrocytic stages and begin to multiply.
Dr. Isabelle Coppens studies how these parasites co-opt host cell processes to support parasite differentiation and replication. She is particularly interested in how the parasite remodels the host cytoskeleton, utilizes the host’s membrane trafficking and salvages host lipids to support its unparalleled replication rate. Mature liver stage parasites enter the bloodstream and inititate the erythrocytic stage of infection. This is the stage responsible for all clinical symptoms of malaria and is the target of all drugs designed to treat the disease.
Dr. Sean Prigge’s laboratory studies the metabolic pathways essential to the blood stage parasites and specifically those contained in the parasite’s two organelles, the apicoplast and the mitochondrion. Because these organelles are of prokaryotic origin, they contain a range of metabolic pathways that differ significantly from those of the human host; specifically those that are dependent on the enzyme cofactors lipoate, biotin and iron-sulfur clusters. When the parasite is growing in red blood cells, it uses host hemoglobin as a source of amino acids and then must detoxify the resulting heme moiety whose reactive iron can kill the parasite.
Dr. David Sullivan’s work is focused on understanding parasite iron metabolism. Dr. Sullivan is also interested in the etiology of the severe anemia that children with malaria can have and is using the rodent model to probe this aspect of infection. During the blood stage of infection, the parasite produces sexual forms that when taken up by an Anopheles mosquito, undergo sexual reproduction in the mosquito midgut to produce ookinetes which penetrate the midgut wall and come to rest on the basal surface of the midgut to produce sporozoites, which ultimately go to the salivary glands to begin the cycle again.