Crucial role in international tumour protein discovery

Posted on June 8, 2011

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The laboratory of La Trobe University scientist Associate Professor John Silke has contributed to an important international discovery which could play a critical role in the treatment of cancers and autoimmune diseases.

The discovery was made during a joint project led by Cancer Research UK funded scientists based at Imperial College London and Dr Andrew Webb and Associate Professor Tony Purcell from Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne.

Central to the study was the finding by the Imperial College team that Sharpin, a protein that controls inflammation, was recruited to the receptor for Tumour Necrosis Factor (TNF).

TNF plays a pivotal role in protecting the body against infection by bacteria, viruses and other pathogens. It does this by directing the immune system to spot rogue pathogens and then destroy them.

However, if unregulated, TNF is also known to cause harm, contributing to unwanted inflammation and autoimmune diseases.

The research team discovered that Sharpin prevents TNF from inducing inflammation, providing new clues to how cancers may be able to ‘hijack’ the immune system.

Associate Professor Silke said the La Trobe laboratory discovered that an inflammatory skin disease in mice lacking Sharpin could be completely resolved by switching off TNF.

‘This was a striking result, not least because TNF-controlled inflammation is central to a wide variety of different diseases from autoimmune diseases – like rheumatoid arthritis and psoriasis – to cancer,’ he said.

The University of Melbourne team developed a state-of-the-art technique, which enabled the international team to identify and characterise the new molecular changes involved in the discovery. 



The next step is to use this new technique to further examine TNF and related pathways, to further understand how these pathways function in a bid to lead to better therapies for diseases that involve immune dysfunction.

The research has been published in Nature.