Malaria breakthrough by Melbourne researchers at Walter and Eliza Hall Institute
Scientists have made a significant step towards developing new malaria drugs, capturing the first three-dimensional image of a “bus conductor” protein that gives the parasite its ticket to survival.
For more than a decade, the Melbourne researchers have been trying to uncover how the malaria parasite invades and takes over the red blood cells of humans.
Walter and Eliza Hall Institute’s Professor Alan Cowman said until now they did not know what the crucial protein that helped the parasite looked like.
“Trying to design a drug to target a protein without knowing the shape is possible, but it’s a bit like working in the dark,” he said.
Their discovery has shone light on the parasite, known as plasmepsin V.
“This parasite basically moves in and renovates the red blood cell,” Prof Cowman said.
“The first step in that process is selecting and exporting other proteins to go in and do the renovations, so the carpenters, plumbers and roofers.”
Not only does the protein subcontract renovation jobs, he said, it also acts as bus conductor, giving the parasite a ticket to the correct destination and validating its ticket.
“Without that conductor protein, the parasite cannot renovate and dies,” Prof Cowman said.
In a new research paper, the WEHI team describes how it created a crystal of the protein and used the Australian Synchrotron in Melbourne to reveal its structure in 3D.
“For the first time, we can see the exact shape of the protein, which is critical for the next step in developing better drugs,” Prof Cowman said.
He said the new finding was a crucial step that would accelerate and redirect their research and development into new drugs to treat and prevent malaria, which half of the world’s population is at risk of contracting.
The search for new malaria drugs and vaccines has become even more critical because the parasite is developing a resistance to many effective treatments.
Colleague Dr Justin Boddey said targeting this protein would effectively kill two species of malaria that caused death and disease.
Researchers have now partnered with a major pharmaceutical company to develop drugs.
The research was published today in Nature Structural and Molecular Biologyjournal.