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Scientists find ‘assassin’ protein that kills rogue cells

For the first time, scientists have discovered an “assassin” protein which attacks and kills rogue cells to protect the human immune system, a breakthrough that can lead to new treatments for a host of diseases, including cancer, malaria and diabetes. Using powerful electron microscopes, a team of Australian and British scientists found how the protein,…

For the first time, scientists have discovered an “assassin” protein which attacks and kills rogue cells to protect the human immune system, a breakthrough that can lead to new treatments for a host of diseases, including cancer, malaria and diabetes.

Using powerful electron microscopes, a team of Australian and British scientists found how the protein, called perforin, adopts a unique mechanism of punching holes in the cells that have become cancerous or infected by viruses.

The the ten-year study, published in journal Nature, is the first to show how perforin plays an important role of cleaning wayward cells that could otherwise cause several life-threatening diseases, including cancer.

Professor Helen Saibil, who led the UK team at Birkbeck College, said: “Perforin is a powerful bullet in the arsenal of our immune system — without it we could not deal with the thousands of rogue cells that turn up in our bodies through our lives.”

“Perforin is our body’s weapon of cleansing and death,” said project leader Professor James Whisstock from Monash University, Melbourne, Australia.

According to the team, perforin works by punching holes in rogue cells that have been “hijacked” by viruses or turned into cancer cells. The holes then allow toxic enzymes into the cells and destroy them.

If perforin isn’t working properly the body can’t fight infected cells. And there is evidence from mouse studies that defective perforin leads to an upsurge in malignancy, particularly leukaemia, said Professor Joe Trapani, head of the Cancer Immunology Program at the Peter MacCallum Cancer Centre in Melbourne.

Professor Saibil said: “From our previous work we already knew that bacterial toxins, such as the one involved in pneumonia, dramatically change shape to punch holes in membranes.

“We were fascinated by perforin and wanted to know its structure and how that might change in order for it to act as a hole-punching machine.”

The scientists, who uncovered the structure and functions of perforin by using high-powered microscope, said the protein shared a number of molecular similarities with bacterial toxins like anthrax, listeria and streptococcus.

According to them, 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 they are now investigating ways to boost perforin for more effective cancer protection and therapy for acute diseases such as cerebral malaria.

“Now we know how it (perforin) works, we can start to fine tune it to fight cancer, malaria and diabetes,” Professor Whisstock added.

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First published on: 01-11-2010 at 17:15 IST
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