Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune system assassin's tricks visualised for the first time

01.11.2010
Scientists from the UK and Australia have seen the human immune system's assassin – a protein called perforin – in action for the first time.

The UK team, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust, is based at Birkbeck College where they used powerful electron microscopes to study the mechanism that perforin uses to punch holes in rogue cells. The research is published today (1800hrs, 31 October) in Nature.

Professor Helen Saibil, who leads 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.

Perforin works by punching holes in cells that have become cancerous or have been invaded by viruses. The holes let toxic enzymes into the cells, which then 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, so says Professor Joe Trapani, head of the Cancer Immunology Program at the Peter MacCallum Cancer Centre in Melbourne, Australia.

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 we have had to wait for the latest advances in structural molecular biology to find out how exactly this happens.

Professor Saibil continued "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 structure was revealed by combining information about a single perforin molecule – visualised using the Australian Synchrotron – with Professor Saibil's electron microscope images, (taken in London), of a ring of perforin molecules clustered together to form a hole in a cell membrane.

Professor Whisstock added "Now we know how it works, we can start to fine tune it to fight cancer, malaria and diabetes."

Another interesting finding is that the important parts of the perforin molecule are quite similar to those toxins deployed by bacteria such as anthrax, listeria and streptococcus, showing that this method of making holes in cell membranes is quite ancient in evolution. "The molecular structure has survived for close to two billion years, we think," said Professor Trapani.

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 £600K grant from the Wellcome Trust they are working on potential inhibitors to suppress perforin and counter tissue rejection.

Professor Douglas Kell, BBSRC Chief Executive said "New technologies in microscopy and synchrotron experiments have opened up tremendous opportunities for molecular biologists. This is a great example where the knowledge we gain about the normal structure and function of a molecule has the potential to underpin important developments in our health and well being."

Contact

BBSRC External Relations
Nancy Mendoza, Tel: 01793 413355, email: nancy.mendoza@bbsrc.ac.uk
Tracey Jewitt, Tel: 01793 414694, email: tracey.jewitt@bbsrc.ac.uk
Mike Davies, Tel: 01793 442042, email: mike.davies@bbsrc.ac.uk
Matt Goode, Tel: 01793 413299, email: matt.goode@bbsrc.ac.uk
Notes to Editors
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. The project leaders are: Joe Trapani (Peter Mac), Helen Saibil (Birkbeck) and James Whisstock (Monash). The research was supported by the above institutions, the NHMRC, the ARC, the UK Biotechnology and Biological Sciences Research Council and the Wellcome Trust.

Feature story/backgrounder and photos available from Niall Byrne at Science in Public, Melbourne, Australia. Tel: +61 417 131 977, email: niall@scienceinpublic.com.au

About BBSRC

The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.

The Babraham Institute, Institute for Animal Health, Institute of Food Research, John Innes Centre and Rothamsted Research are Institutes of BBSRC. The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.

Nancy Mendoza | EurekAlert!
Further information:
http://www.bbsrc.ac.uk

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>