Navigation Links
How do we kill rogue cells?

A team of Melbourne and London researchers have shown how a protein called perforin punches holes in, and kills, rogue cells in our bodies. Their discovery of the mechanism of this assassin is published today in the science journal Nature.

"Perforin is our body's weapon of cleansing and death," says project leader Prof James Whisstock from Monash University.

"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," he says.

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. But how?

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 perforinthe 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," says Prof Joe Trapani, head of the Cancer Immunology Program at Peter Mac.

"This work is a dramatic illustration of the importance of the synchrotron," says Whisstock. "We simply couldn't have done it without this wonderful facility."

The weapon of death is a powerful molecule. If perforin isn't working properly the body can't fight infected cells. And there is evidence from mouse studies, says Trapani, 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.

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


Contact: Niall Byrne
Science in Public

Related biology news :

1. Oregons Rogue River Basin to face climate-change hurdles
2. iGEM team helps prevent rogue use of synthetic biology
3. Does the existing standard of care supply energy sources to brain tumor cells?
Post Your Comments:
(Date:10/29/2015)... Oct. 29, 2015 Today, LifeBEAM ... partnership with 2XU, a global leader in technical ... smart hat with advanced bio-sensing technology. The hat ... to monitor key biometrics to improve overall training ... the two companies will bring together the most advanced ...
(Date:10/27/2015)... SAN JOSE, Calif. , Oct. 27, 2015 /PRNewswire/ ... human interface solutions, today announced that Google has adopted ... family of touch controller solutions to power its newest ... Nexus 6P by Huawei. --> ... ecosystem partners like Google to provide strategic collaboration in ...
(Date:10/26/2015)... 26, 2015  Delta ID Inc., a company focused ... and PC devices, announced its ActiveIRIS® technology powers the ... F-02H launched by NTT DOCOMO, INC in ... second smartphone to include iris recognition technology, after a ... F-04G in May 2015, world,s first smartphone to have ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... PUNE, India , November 26, 2015 /PRNewswire/ ... The Global Biobanking Market 2016 - 2020 ... biobanks by maintaining integrity and quality in long-term ... and enabling long-term cost-effectiveness. Automation minimizes manual errors ... improves the technical efficiency. Further, it plays a ...
(Date:11/25/2015)... and HOLLISTON, Mass. , ... Inc. (Nasdaq: HART ), a biotechnology company developing ... CEO Jim McGorry will present at the ... 1, 2015 at 2:30 p.m. PT. The presentation will ... for 30 days. Management will also be available at ...
(Date:11/25/2015)... 25, 2015 Orexigen® Therapeutics, Inc. (Nasdaq: ... a fireside chat discussion at the Piper Jaffray 27th ... . The discussion is scheduled for Wednesday, December 2, ... .  A replay will be available for 14 days ... , Julie NormartVP, Corporate Communications and Business Development , ...
(Date:11/24/2015)... ... 2015 , ... The United States Golf Association (USGA) today announced Dr. Bruce ... Presented annually since 1961, the USGA Green Section Award recognizes an individual’s distinguished service ... , Clarke, of Iselin, N.J., is an extension specialist of turfgrass pathology in the ...
Breaking Biology Technology: