Satish Mishra, Ph. D.

Principal Scientist, Molecular Parasitology and Immunology

Pre-erythrocytic stages of Plasmodium parasites: Basic Biology and
Functional Drug targeting approaches.

Malaria infection begins when an infected female Anopheles mosquito bites a person, injecting Plasmodium parasites, in the form of sporozoites. Sporozoites are formed in the midgut of mosquito, where they emerge from oocysts and reaches salivary gland. Minutes after mosquito bite, malaria sporozoites enter hepatocytes. During the liver stage, a single Plasmodium sporozoite invade a hepatocyte, and gives rise to thousands of merozoites, which initiate blood stage infection. Using reverse genetic approaches, biochemistry and in vitro and in vivo assays, we aim to elucidate the mechanism of host cell invasion and molecular interactions between the parasite and mammalian hosts.

Nearly half the world's population lives in areas at risk of malaria transmission in 91 countries and territories. About 200 million cases and 400,000 deaths are reported annually due to malaria worldwide. The current challenges in curtailing malaria include a lack of effective vaccines and drugs that can target multiple life cycle stages.

Using a rodent malaria model Plasmodium berghei we have established that desaturation of fatty acid in liver stages is essential for the membrane biogenesis and initiation of blood stage infection. Currently, we are analysing the merosome formation in hepatocyte and are interested in parasite-mediated fatty acid modification.

Another goal is to identify new Plasmodium genes essential for liver stage development and are potential targets for intervention. We are generating regular or conditional mutant of genes which are specifically upregulated in sporozoites and dissecting their phenotype. The long-term goal is to identify essential proteins required for progression through the pre-erythrocytic stage and validate them as drug targets.

More recently, we have started addressing the glideosome complex in sporozoites. We have established that some Plasmodium hypothetical proteins are component of the innermembrane complex and now we are looking if these are part of the glideosome complex in sporozoites.