Protein key to malaria parasite’s lifecycle

New research suggests that a regulator protein, AP2-G, may hold the key to finding new approaches to prevent malaria.

The team behind the work, from the University of Glasgow and the Wellcome Sanger Institute, designed a new experimental system to investigate, in detail, the role of AP2-G in the Plasmodium parasite’s life. Scientists found that AP2-G is the master switch in the parasite that controls a pattern of gene expression essential for the parasite to successfully infect mosquitoes.

Professor Andy Waters, Director of the Wellcome Centre for Molecular Parasitology at the University of Glasgow, said: “This new experimental approach enabled us to confirm that AP2-G controls vitally important developmental pathways in gametocytes, and that it controls further gene expression and development.

“We also showed that both male and female specific genes are expressed and that blocking the expression of one of these genes resulted in parasites that could not make male gametocytes, thus ending the parasite lifecycle. Foremost, our work has the potential to uncover further novel biology as well as strategies that will prevent the spread of this devastating disease.”

The Plasmodium parasite has a complex lifecycle, which relies on a cycle of transmission between humans and mosquitoes. The disease-causing forms grow asexually inside red blood cells of an infected human host. These forms are not infectious to mosquitoes. At a key stage in the lifecycle, specialised forms of the parasites called gametocytes are produced in the blood. These gametocytes exist as male and female forms and they can initiate the mosquito phase of the parasite life cycle when they get taken up by a female mosquito biting an infected human.

Dr Oliver Billker, from the Wellcome Sanger Institute, said: “What led us to the breakthrough was that we designed a new experimental parasite line in which we could dial the amount of AP2-G up and down. By dialing AP2-G up, we managed to turn all blood stage parasites into parasites that were able to infect mosquitoes.

The work is published in Nature Microbiology.