I. Siden-Kiamos Laboratory

Plasmodium gametocytes (red) residing inside red blood cells (green) surrounded by non-infected red blood cells (green)

Our research focuses on malaria parasites. The primary reason is that malaria remains a devastating disease leading to 250-400 million infections and approximately half a million deaths every year, mostly of young children in sub-Saharan Africa. Together with economic loss associated with the disease, these figures contribute to a dramatic developmental slowdown in some of the poorest countries in the world. Researchers in the malaria field are all strongly motivated by these facts, with the overall goal to improve, directly or indirectly, available strategies for intervention and/or to develop novel approaches. The aim of our laboratory is on the one hand the understanding of basic cell biology of the parasite, which in the long term may contribute to this goal. Secondly, we also contribute directly to the development of novel approaches to target the disease.

Plasmodium parasites are transmitted by mosquitoes of the genus Anopheles and we mainly study the stages of the parasite in the mosquito. Today the mosquito stages are recognized as a priority area for research on malaria parasites, as it is recognized that elimination and eradication of this complex pathogen can only be achieved if the mosquito stages are also targeted. The parasite resides in the mosquito for about three weeks and during this time a complex series of developmental changes take place. The mosquito stages and the transition between the different forms involve cellular processes which are not well studied. Our studies have contributed to a better understanding of several important processes taking place during parasite development in the mosquito. We use a combination of approaches: reverse genetics, biochemical methods, advanced microscopy and structural studies. We collaborate with a number of internationally renowned groups, something which is critical as this area of research is competitive and challenging.

Parasite stages in the mosquito
Parasites enter the vector as intraerythocytic male and female gamete precursors (gametocytes) via an infected blood meal. Within minutes the gametocytes are activated and fertilisation takes place leading to the formation of a zygote. In the next few hours, the zygote transforms to a motile invasive ookinete that traverses the midgut epithelium and forms an oocyst on the haemocoel side of the midgut. During the next ~10 days sporozoites develop in a syncytium inside the oocyst, which is delimited by the oocyst capsule. When mature sporozoites have formed, the oocyst ruptures and releases the sporozoites which next transfer to the salivary gland. They will then be injected into the skin of the mammalian host when the mosquito bites. The sporozoites first develop in hepatocytes and form merozoites; these are the invasive forms for the red blood cells. As merozoites are released they invade erythrocytes and initiate replicative asexual blood stage infections, which occasionally lead to the formation of the gametocytes.