Unearthing immune responses to common drugs

Australian researchers are a step closer to understanding immune sensitivities to well-known, and commonly prescribed, medications.

Many drugs are successfully used to treat diseases, but can also have harmful side effects. While it has been known that some drugs can unpredictably impact on the functioning of the immune system, our understanding of this process has been unclear.

The team investigated what drugs might activate a specialised type of immune cell, the MAIT cell (Mucosal associated invariant T cell). They found that some drugs prevented the MAIT cells from detecting infections (their main role in our immune system), while other drugs activated the immune system, which may be undesirable.

The results, published today in Nature Immunology, may lead to a much better understanding of, and an explanation for, immune reactions by some people to certain kinds of drugs. The findings may also offer a way to control the actions of MAIT cells in certain illnesses for more positive patient outcomes.

The multidisciplinary team of researchers are part of the ARC Centre of Excellence in Advanced Molecular Imaging, and stem from Monash University, The University of Melbourne and The University of Queensland. Access to national research infrastructure, including the Australian synchrotron, was instrumental to the success of this Australian research team.

Dr Andrew Keller from Monash University’s Biomedicine Discovery Institute said that T cells are an integral part of the body’s immune system.

“They protect the body by ‘checking’ other cells for signs of infection and activating the immune system when they detect an invader,” he said.

“This arrangement is dependent on both the T cells knowing what they’re looking for, and the other cells in the body giving them useful information.”

PhD student Weijun Xu from The University of Queensland’s Institute for Molecular Bioscience used computer modelling to predict chemical structures, drugs and drug-like molecules that might impact on MAIT cell function. Such small compounds included salicylates, non-steroidal anti-inflammatory drugs like diclofenac, and drug metabolites.

University of Melbourne Dr Sidonia Eckle from the Peter Doherty Institute for Infection and Immunity said the implications point to possible links between known drug hypersensitivities and MAIT cells.

“A greater understanding of the interaction between MAIT cells and other host cells will hopefully allow us to better predict and avoid therapeutics that influence and cause harm,” she said.

“It also offers the tantalising prospect of future therapies that manipulate MAIT cell behaviour, for example, by enhancing or suppressing immune responses to achieve beneficial clinical outcome.”

Image credit : Vanette Tran

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2016 Victoria Prize for Science & Innovation

The Victoria Prize for Science and Innovation recognises the outstanding work of established Victorian scientists and the impact of their research.
Prof Jamie Rossjohn, of Monash University, and Prof James McCluskey, Deputy Vice-Chancellor (Research) at University of Melbourne, last night received the Victoria Prize for Science and Innovation for 15 years of pioneering work in understanding of how T lymphocytes from the immune system recognise harmful microbes.
Their research aims to build better vaccines, diagnosis and treatment of inflammatory bowel disease, peptic ulcers and tuberculosis.

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PM opens Monash Biomedicine Discovery Institute and visits Rossjohn Lab

Australia’s capacity to deliver innovative solutions to critical global health problems has been enhanced with the development of Monash University’s Biomedicine Discovery Institute (BDI) which was officially opened today by Prime Minister the Hon. Malcolm Turnbull MP.

Monash University’s President and Vice-Chancellor, Professor Margaret Gardner AO, welcomed Prime Minister Turnbull to the launch of the Monash BDI, which brings together a collaborative research effort of great scale that will see more than 120 world-renowned research teams, 700 on site researchers,  clinical partners and industry working together. The Monash BDI will be located at Monash’s Clayton campus where it will form a key part of the innovation precinct delivering crucial economic and social benefits to Victoria and the nation.

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Jamie awarded the ARC Australian Laureate Fellowship

Professor Jamie Rossjohn has been awarded a highly prestigious Australian Laureate Fellowship from theAustralian Research Council, worth $2.9 million over five years.

NHMRC Australia Fellow, Professor Jamie Rossjohn, from the Biomedicine Discovery Institute, was announced as a recipient of the 2016 Australian Laureate Fellowship at a ceremony in Canberra on Friday.

This fellowship will help Professor Rossjohn to continue his research into how key immune recognition events enable immunity.

Professor Rossjohn said his project would be supported by the cross-disciplinary approaches within the ARC Centre of Excellence in Advanced Molecular Imaging, key platform technologies at Monash and the Australian Synchrotron.

“This recognition is always a consequence of a team effort – students and researchers of the laboratory, collaborators, and Monash University,” Professor Rossjohn said.

“I would like to acknowledge the support of the ARC team within the Monash Research Office – they were superb in ensuring my application was in the best possible shape,” he said.

Most recognised for his contributions to understanding the function and dysfunction of the immune system, Professor Rossjohn has provided profound insight into T-cell biology. He has used structural biology to explain T-cell development and pioneered our understanding of lipid-based immunity by T-cells, recently showing how vitamin B metabolites represent an entirely new and important target for the immune system.

The Minister for Education and Training, Simon Birmingham, on Friday announced the Australian Research Council Laureate Fellowships at the ceremony in Canberra.

“We must continue to encourage not only the brightest Australian minds to explore opportunities here, but also to attract the best from overseas to share their knowledge in Australia,” Senator Birmingham said.

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Jamie and Jim awarded the GSK Award for Research Excellence

A research partnership between The University of Melbourne and Monash University has won $80,000 to help continue groundbreaking work on how the immune system identifies and fights disease. The research could assist the treatment of inflammatory bowel disease, peptic ulcers, tuberculosis and lead to better vaccines. The successful team, led by Professors James McCluskey and Jamie Rossjohn, has won the GSK Award for Research Excellence announced last night at the Research Australia Annual Awards.

Professors McCluskey and Rossjohn have uncovered insights into how the immune system recognises pathogens (harmful germs) such as salmonella and tuberculosis. The surprising discovery reveals how the making of Vitamin B2 by microbes could lead to how our immune system recognises these pathogens. This research could be the starting point in better understanding our body’s first line of defence.

Professor James McCluskey explains that their recent breakthrough shows how the immune system uses the building blocks in Vitamin B2 production to recognise bacteria.

“Bacteria, not humans, manufacture vitamins, which is why we rely on our diet to provide vitamins. We have learnt that the manufacture of vitamin B2 or riboflavin, plays an extremely important and protective role in alerting the immune system to foreign bacteria,” he said.

“This work is but the tip of the iceberg in understanding the role of certain cells in the immune system,” McCluskey said.

“It’s a great example of curiosity-led science and could lead to new ways of diagnosing and treating inflammatory bowel disease, peptic ulcers and even tuberculosis – it could also lead to novel protective vaccines.”

Professor Jamie Rossjohn says winning the GSK Award for Research Excellence will help both teams nurture new talent in their laboratories and play an important role in publicising their long-term work.

“Winning the GSK Award for Research Excellence places our work in the public eye. It’s early days, but the public can rest assured that our teams are working extremely hard to see where this discovery will take us. The best fundamental science will lead to the best innovative therapeutics,” he said.

Geoff McDonald, GSK Australia Vice President and General Manager, says GSK is very proud to be able to support local researchers with the Award, now in its 35th year.

“It is a great honour to be able to assist outstanding researchers with this award,” he said.

“Research and development is all about inquisitiveness and innovation. Key new insights like this along the path to discovery are of great importance and need to be encouraged and supported.”

The GSK Award for Research Excellence was presented at the Research Australia Annual Award, Park Hyatt, Melbourne.

Pictured (L-R): Geoff McDonald, VP and General Manager GSK, Professor James McCluskey, Professor Jamie Rossjohn and Andrew Weekes, Medical Director GSK.

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