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26 October 2009
Research into immunity and infection at Cardiff University has been given a multi-million pound boost with a major award from the Biotechnology and Biological Sciences Research Council (BBSRC).
An internationally recognised team from the School of Medicine, led by Professor Andy Sewell, will further their world-leading work into T-cells after being awarded £3M by the BBSRC.
T-cells perform essential roles in the human immune system. They control and protect us from infection, are vital in the natural eradication of cancer and hold the key to successful vaccinations.
T-cells can also malfunction and when this occurs, they are believed to cause autoimmune diseases such as diabetes, rheumatoid arthritis and multiple sclerosis. Autoimmunity is typically chronic, progressively debilitating and cannot be cured and these diseases generate huge human and financial costs.
The £3M award will allow Professor Sewell and his team to examine how individual T-cells recognise huge numbers of foreign antigens (known as cross-reactivity). This essential cross-reactivity is enabled because the receptor molecule on the T-cell surface is highly promiscuous and can recognise many similar molecular ‘shapes’.
While T-cell receptor promiscuity allows our T-cells to control infection it is also thought to be responsible for the harmful effects these cells can sometimes cause. Autoimmunity is believed to arise when a receptor that is raised to fight infection is inadvertently promiscuous enough to recognize our own tissues. This promiscuous receptor recognition can also result in allergic reactions and is responsible for why our immune cells attack a ‘foreign’ organ in the first week after it is transplanted.
Explaining the need for this research, Professor Sewell said: "T-cell receptor promiscuity sits at the very heart of most human health. Despite its obvious importance, there has never yet been a proper attempt to examine or assess this promiscuity and the T-cell cross-reactivity it enables. New tools developed by the Cardiff team have finally provided the keys to unlock this study and make this research especially timely.
"Basic biological research is vital for later clinical applications but this is one of those areas where the possibilities for translation are clear from the outset. As such, we anticipate that this work will generate valuable spin offs that improve clinical practice in addition to furthering our understanding of the very interaction that orchestrates human immunity."
Professor Janet Allen, Director of Research, BBSRC, said: "Fundamental bioscience research is vital to underpin advances in medicine and healthcare. By understanding processes that lie at the very core of how our bodies function, such as T-cell receptor promiscuity, researchers can go on to use the knowledge to develop new treatments and therapies for a wide range of diseases."
Professor Sewell and his team have a long history in T-cell research. They have already helped engineer T-cell receptors that can recognise all the different disguises that HIV is known to have used to evade detection. The genetically engineered cells were able to destroy HIV-infected cells in culture and clinical trials are just starting.
Professor Sewell added: "The potential applications and benefits of this work are immense. We have already built T-cell receptors that are promiscuous enough to see all known immune escape variants of the HIV virus. We have further built receptors that have better ‘shapes’ for detecting and eliminating cancer. In addition, we expect that this work will revolutionise vaccination and provide insights into the blight of autoimmune disease."
BBSRC is the main UK public funder of bioscience research. It invests around £450M a year in cutting edge science and training that helps to support the national quality of life and the UK economy by underpinning developments in healthcare, pharmaceuticals, food and agriculture.
The Cardiff team now incorporates the clinical expertise in infectious diseases of Professor David Price, the veterinary background of Dr. Linda Wooldridge in addition to Dr. Pierre Rizkallah, a physicist who specializes in protein crystallography. Hugo van den Berg from the Warwick Systems Biology Centre will assist this multi-disciplinary team with data analysis. The group will start work on the new research in November 2009.
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