Protein export to hijack human cells during liver-stage malaria

Protein export to hijack human cells during liver-stage malaria

Project details

Each year more than 200 million malaria cases occur resulting in more than 500,000 deaths. Malaria parasites injected by mosquitoes infect the liver before red blood cells yet we understand little about this process (Boddey and Cowman, Annual Review of Microbiology 201367: 243-269).

We have identified a new pathway the targets malaria proteins into infected hepatocytes. This project will use the Institute’s insectary to study the role of exported parasite proteins in hijacking liver cells. This will involve modifying the malaria genome to create mutant parasites, measuring infection of human liver cells and other in vivo models by mutant sporozoites, localizing virulence proteins in mutants by super resolution microscopy and studying the effects of parasite proteins on halting host cell apoptosis, which is essential for malaria parasite development in the liver. 

About our research group

Our laboratory is interested in understanding the molecular basis of how malaria parasites infect mosquitoes as this allows the widespread transmission of this devastating disease. We are also interested in understanding how parasites injected by mosquitoes infect the human liver. 

Previous studies have proven that genetically weakened liver-stage parasites are destroyed by the immune system. This provides protective immunity and therefore could deliver the first malaria vaccine. The mosquito and liver stages of malaria therefore provide exciting opportunities to block the spread of malaria and to develop an urgently needed vaccine for this disease.

 

Malaria life cycle diagram
During infection of the human liver malaria parasites live within a vacuole (red) and express plasmepsin V (green) to control protein export.

 

Researchers:

Dr Justin Boddey

Dr Justin Boddey in the lab
Dr
Justin
Boddey
Laboratory Head

Professor Alan Cowman

Professor Alan Cowman in the lab
Professor
Alan
Cowman
Deputy Director and Joint Division Head

Project Type: