Researchers view malaria in action for the first time

Composite showing, at nanometer scales, the behaviour of the malaria parasite at each stage of red blood cell invasion (attachment, invasion, sealing). The three components of the parasite are fluorescently labelled (blue = parasite nucleus, red = secretory organelle, green = tight junction) with the red blood cell shown in grey. (Image: WEHI)

The Plasmodium parasite responsible for malaria leads a notoriously complex lifecycle, with one of the key stages in humans involving the infection of red blood cells.

Now, for the first time, researchers at the Walter and Eliza Hall Institute (WEHI) in Melbourne working in collaboration with the ithree institute at the University of Technology Sydney have captured detailed images of the parasite in the process of invading blood cells.

Read more about malaria.

These images will give scientists an unprecedented view of how the parasite burrows through cell walls and gives insights into the molecular and cellular events that drive cell invasion.

The researchers, led by the WEHI's Dr Jake Baum, Mr David Riglar and Dr Dave Richard, believe this breakthrough could lead to new malaria treatments as well as new methods for evaluating the effectiveness of experimental anti-malaria drugs.

“It is the first time we’ve been able to actually visualise this process in all its molecular glory, combining new advances developed at the institute for isolating viable parasites with innovative imaging technologies,” said Baum.

The teams used the latest in super resolution microscopy, which breaks the diffraction limit, or 'light barrier,' and allows smaller objects to be seen than with conventional light microscopes.

They collaborated with Associate Professor Cynthia Whitchurch and Dr Lynne Turnbull from the ithree institute who used their OMX 3D SIM super resolution microscope to capture images of the parasite at the nanometre scale.

“This is just the beginning of an exciting new era of discoveries enabled by this technology that will lead to a better understanding of how microbes such as malaria, bacteria and viruses cause infectious disease,” Whitchurch said.

One of the things discovered by the researchers was that once the parasite has attached to the red blood cell and formed a tight bond with the cell, a master switch for invasion is initiated and invasion will continue unabated without any further checkpoints.

"The parasite actually inserts its own window into the cell, which it then opens and uses to walk into the cell, which is quite extraordinary,” Dr Baum said.

“Visually tracking the invasion of Plasmodium falciparum into a red blood cell is something I’ve been aiming at ever since I began at the Walter and Eliza Hall Institute in 2003; it’s really thrilling to have reached that goal. This technology enables us to look at individual proteins that we always knew were involved in invasion, but we never knew what they did or where they were, and that, we believe, is a real leap for malaria researchers worldwide,” said Baum.

Baum said the methodology would be integral to the development of new malaria drugs and vaccines. “If, for example, you wanted to test a particular drug or vaccine, or investigate how a particular human antibody works to protect you from malaria, this imaging approach now gives us a window to see the actual effects that each reagent or antibody has on the precise steps of invasion,” he said.

Around 400 million people contract malaria each year, mainly in developing countries, exerting a crippling social and economic impact on those countries.

A recent World Health Organization report found that malaria control techniques have slowed the spread of the disease, but researchers believe it will only be eradicated once we develop a vaccine.

The research was published in the journal Cell Host & Microbe.

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