Immune sentries protect gut from bugs by sensing vitamins

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Dr Ligong Liu and Dr Jeffrey Mak

Australian researchers have identified a biochemical key that alerts immune cells to the presence of bacteria and fungi, which could lead to new ways of diagnosing and treating diseases such as inflammatory bowel disease, peptic ulcers and even infections like tuberculosis.

The discovery, made by scientists from the Universities of Queensland, Melbourne, Monash and Cork, provides a starting point for understanding a human’s first line of immune defence and what causes it to go wrong in disease.

The team had previously found that a type of immune cell, known as mucosal-associated invariant T cells (MAITs), could detect molecules produced by bacteria and fungi when manufacturing vitamin B2, also known as riboflavin.

Bacteria synthesise vitamin B2 for their growth whereas humans are unable to make this vitamin.

The researchers have now pinpointed the exact chemicals that activate these special human immune cells, which act as red flags to the immune system.

Professor David Fairlie, from UQ’s Institute for Molecular Bioscience, said this finding may be very important for understanding the body’s reaction to some bacterial infections.

“Essentially this is a way of sensing the presence of bacteria and mounting an immune response, without interfering with nutrition,” Professor Fairlie said.

“This may be a valuable clue to previously unknown mechanisms of immunity and possibly disease pathology, and could lead to entirely new drug development strategies.

He acknowledged Dr Ligong Liu and Dr Jeff Mak, also from UQ’s Institute for Molecular Bioscience, who synthesised and isolated the unstable chemicals that trigger activation of these T cells.

Other senior authors on the paper, published overnight in world-leading scientific journal Nature, were Professor Jim McCluskey from The University of Melbourne and Professor Jamie Rossjohn from Monash University.

“This is an excellent example of how collaborative research in Australia can bring groups with expertise in different areas together to make significant advances,” Professor McCluskey, Deputy Vice-Chancellor (Research) of The University of Melbourne, said.

The work is an early win for the recently announced Australian Research Council Centre of Excellence in Advanced Molecular Imaging.

“We want to unravel the complex molecular interactions that define how we fight disease,” Professor Rossjohn said.

“This remarkable research collaboration shows us how to do it.”

Media contact: IMB Communications Manager Bronwyn Adams, 0418 575 247, 07 3346 2134,b.adams@imb.uq.edu.au

Global collaboration targets drug-resistant parasites

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April 2014

Researchers from The University of Queensland and Griffith University have teamed with scientists from Europe and South America to develop new treatments for drug-resistant parasitic infections.

The international effort will combat malaria, schistosomiasis, leishmaniases and trypanosomiasis (sleeping sickness), which each year kill more than a million people worldwide as the parasites that cause these diseases increasingly become resistant to treatments.

The AUD$7.5 million project will discover, evaluate and develop new drugs to target key proteins essential for the growth of the parasites that spread these infections and that are transmitted to humans by mosquitoes, freshwater snails, sand flies and tsetse flies.

Professor David Fairlie from UQ’s Institute for Molecular Bioscience said an international collaboration to focus on the parasites responsible would have the best chance at advancing cures for these diseases.

“This is a fantastic opportunity for chemists, biochemists, parasitologists and industry to use shared resources in finding new treatments that can improve the lives of hundreds of millions of people around the globe afflicted by these infections,” Professor Fairlie said.

Associate Professor Katherine Andrews from Griffith’s Eskitis Institute for Drug Discovery said the growing ineffectiveness of current medications was an emerging global problem.

“Effective new drugs are desperately needed and this multinational collaborative program has the potential to deliver exciting new drug leads and important information to help develop them for therapeutic application,” Associate Professor Andrews said.

The Australian National Health and Medical Research Council has funded the Australian scientists’ participation in the study, which is sponsored by the European Union and involves a consortium of researchers from Australia, France, Germany, Italy, Sweden, the UK, and Brazil.

Media: Griffith University Communications Manager Helen Wright: 0478 406 565,helen.wright@griffith.edu.au

ARC Centre of Excellence Success

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Congratulations to Professor David Fairlie who was awarded an ARC Centre of Excellence in Advanced Molecular Imaging grant, with funding commencing this year. The CoE application was led by Monash.

David is one of 10 CIs from physics, chemistry, structural biology and immunology who will be working together to develop innovative imaging technologies and applying them to better understand the molecular basis of immunity and the interplay of immunological proteins.

New drug lead shows promise as potential treatment for obesity

23 August 2013

Scientists from The University of Queensland have discovered a new drug lead that prevents rats on a high-fat, high-sugar diet from becoming obese.

Professor David Fairlie, from UQ’s Institute for Molecular Bioscience, led the study, which provides strong evidence that drugs designed to treat inflammatory diseases may also be able to prevent and treat obesity.

“Obesity and diabetes have reached epidemic proportions in both adults and children,” Professor Fairlie said.

“The clear need for new treatments, combined with the hypothesis that obesity is actually an inflammatory disease, prompted us to study one of our anti-inflammatory compounds for its capacity to prevent and treat obesity in rats.”

http://fairlie.imb.uq.edu.au/index.php?id=27