The benefits of perforin revealed

A team of Melbourne and London researchers have shown how a protein called perforin punches holes in and kills rogue cells in the human body.

Professor James Whisstock from Monash University said that perforin is our body’s weapon of cleansing and death.

"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," Professor Whisstock said.

The first observations that the human immune system could punch holes in target cells were made by the Nobel Prize winner, Jules Bordet over 110 years ago.

Researchers from the Peter MacCallum Cancer Centre in Melbourne, Monash University and Birkbeck College in London collaborated on the ten year study to unravel the molecular structure and function of perforin, the protein responsible.

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.

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.

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.

The researchers are now investigating ways to boost perforin for more effective cancer protection and therapy for acute viral diseases such as cerebral malaria.

The lead authors are Ruby Law from Monash University, Natalya Lukoyanova from Birkbeck College, London, and Ilia Voskoboinik from the Peter MacCallum Cancer Centre and the University of Melbourne.

Further information

The discovery has been published in the science journal Nature. Further information including background information and photos is available from the Science in Public website.