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CHEMICAL engineers at the UK’s University of Cambridge have collaborated with teams of physicists and physiologists to shed new light on how malaria spreads.

Using advanced laser microscopy techniques the researchers were able to follow in detail how individual blood cells become infected by the Plasmodium falciparum parasite – the most deadly form of malaria. Once the parasites, at this stage called merozoites, enter blood cells they develop and multiply, quickly infecting neighbouring cells.

“A huge amount of research has been devoted to understanding the [blood cell] penetration process,” says Cambridge biologist Teresa Tiffert. “The focus of many vaccine efforts is the molecules on the surfaces of both parasite and red cell that are instrumental in recognition and penetration.

“But the pre-invasion stage, when a merozoite first contacts a cell targeted for invasion, remained a profound mystery.”

The merozoites are only in the bloodstream for less than two minutes before invading a blood cell, and in order to work out how the penetration begins, the team needed to record it at high speed, using heavy magnification and variable focussing in three dimensions.

“And the real challenge is to have the microscope on the right settings and to be recording at exactly the time when an infected cell has burst and released merozoites,” adds Tiffert. “Something that is impossible to predict.”

In order to work out exactly what was going on, Tiffert and her fellow biologists sought help from chemical engineering professor and bio-imaging specialist Clemens Kaminski, as well as physicist Pietro Cicuta. Together, they established a completely automated imaging system that they claim “pushes the boundaries of live cell imaging,” enabling the researchers to observe individual cells and merozoites throughout the process of infection.

“This microscope can not only run by itself for days, it can perform all the tasks that a human would otherwise be doing,” explains Cicuta. “It can refocus, it can find infected cells and zoom in, and when it detects a release of parasites it can change its imaging modality by going into a high frame-rate acquisition. And when the release has finished it can search around in the culture to find another cell to monitor automatically.”

The researchers say that the new microscope should be “an extraordinary new tool” for designing anti-malarial drugs and vaccines. So far, the researchers have been able to capture around 50 videos of the infection process, which show that the blood cells undergo large changes in shape when the merozoites touch them.

“We’ve also seen very strange shape changes just before the parasites come out of the cells,” adds Cicuta, “and we want to see whether this has a bearing on the parasites’ ability to infect subsequent cells.”

Malaria is caused by parasites transmitted to humans through the bites of infected mosquitoes. According to the World Malaria Report 2011, there were about 216m cases of malaria causing an estimated 655,000 deaths in 2010. Over recent years the P. falciparum parasite has become of particular concern, as it is becoming increasingly resistant to available drugs.