Using millions of microscope images magnified up to 130,000 times, researchers from Radboud university medical center and Toronto have unraveled the structure of two key proteins in the malaria parasite. With this knowledge, scientists are developing new vaccines that block the transmission of parasites via mosquitoes.
Malaria, a parasitic infectious disease, has existed since the time of the ancient Egyptians and still threatens nearly half of the world's population. In recent years, two malaria vaccines have become available that protect against infection, but they do not offer complete protection. Moreover, these vaccines do not stop the spread of the malaria parasite from one person to another via mosquitoes. That's why researchers are working on new vaccines that do block this transmission.
Thirty billion parasites
These new vaccines mainly target two proteins of the malaria parasite. 'These proteins were discovered back in the 1980s, but we still didn't really know what they looked like', says PhD candidate Ezra Bekkering from Radboudumc. 'That's because they're difficult to produce.' Bekkering and his colleagues, together with scientists from The Hospital for Sick Children Research Institute in Toronto, have now finally unraveled the structures of these two proteins and published their findings in the journal Immunity.
To analyze them, the researchers needed to obtain enough of the proteins. To do this, they cultured thirty billion malaria parasites—a process that took six months. They extracted the proteins from the parasites and then resolved their 3D structure using cryo-electron microscopy. This technique allows proteins to be visualised at the atomic level by taking millions of images with a microscope that can zoom in up to 130,000 times.
Sexual reproduction
Although the structure of the proteins is now elucidated, their role remains somewhat mysterious. Researcher Matthijs Jore explains: 'They are part of a complex on the surface of the malaria parasite and are specific to this pathogen. That makes them a suitable target for vaccines. These proteins likely help the parasite during sexual reproduction.'
Now that researchers know the 3D structure of the two proteins, they better understand how the malaria parasite infects mosquitoes and how antibodies against these proteins can block parasite development in the mosquito. They can now use the structure as a blueprint to develop new malaria vaccines that contribute to eradicating this deadly disease. Jore adds: 'If you don't know what something looks like, it's hard to protect yourself against it. The elucidated structures offer new opportunities for better malaria vaccines.'
