AAP
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SYDNEY, Nov 1 AAP - A protein called perforin that kills rogue cells in the human body may a breakthrough in the fight against cancer and diabetes, researchers say.
A team of Melbourne and London researchers have shown perforin punches holes in, and kills, rogue cells in our bodies.
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Their discovery of the mechanism is published on Monday in the science journal Nature.
"Perforin is our body's weapon of cleansing and death," Monash University professor James Whisstock said.
"It breaks into cells that have been hijacked by viruses or turned into cancer cells and allows toxic enzymes in, to destroy the cell from within.
"Without it our immune system can't destroy these cells. Now we know how it works, we can start to fine tune it to fight cancer, malaria and diabetes."
The first observations that the human immune system could punch holes in target cells was made by the Nobel laureate Jules Bordet over 110 years ago.
The researchers from Monash University and the Peter MacCallum Cancer Centre in Melbourne, and Birkbeck College in London, collaborated on the ten-year study to unravel the molecular structure and function of perforin, the protein responsible.
The structure was revealed with the help of the Australian Synchrotron, and with powerful electron microscopes at Birkbeck.
Combining the detailed structure of a single perforin molecule with the electron microscopy reconstruction of a ring of perforins forming a hole in a model membrane reveals how this protein assembles to punch holes in cell membranes.
The new research has confirmed that the important parts of the perforin molecule are quite similar to those in toxins deployed by bacteria such as anthrax, listeria and streptococcus.
"The molecular structure has survived for close to two billion years, we think," head of cancer immunology at the Peter MacCallum Cancer Centre, Professor Joe Trapani, said.
Perforin is also the culprit when the wrong cells are marked for elimination, either in autoimmune disease conditions, such as early onset diabetes, or in tissue rejection following bone marrow transplantation.
So the researchers are now investigating ways to boost perforin for more effective cancer protection, and therapy for acute diseases such as cerebral malaria.
With the help of a $1 million grant from the Wellcome Trust they are working on potential inhibitors to suppress perforin and counter tissue rejection.
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