Research into why one fifth of deaths following stroke are from infections, and an ‘unconventional’ approach to TB given a boost by CSL

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Australian researchers looking into why so many people die from infection following stroke and how we might develop better vaccines against diseases such as tuberculosis have both been awarded prestigious CSL Centenary Fellowships. Dr Connie Wong from Monash University’s Centre for Inflammatory Diseases wants to understand why as many as one fifth of deaths following stroke are caused by pneumonia and other infections. Dr Daniel Pellicci from the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, and Murdoch Children’s Research Institute wants to recruit specialist white blood cells, known as ‘unconventional T-cells’ in the fight against tuberculosis (TB).

Organisation/s: CSL Limited

Media Release

From: CSL Limited

Two Australian scientists have each been awarded an AUD$1.25 million, five-year, CSL Centenary Fellowship to further research into why so many people die from infection following stroke and how we might develop better vaccines against diseases such as tuberculosis.

Dr Connie Wong and Dr Daniel Pellicci will be funded through the $25 million CSL Centenary Fellowships program, which was established in 2016 to support mid-career Australian scientists to pursue world-class medical research.

Dr Connie Wong from Monash University’s Centre for Inflammatory Diseases wants to understand why as many as one fifth of deaths following stroke are caused by pneumonia and other infections.

Connie and her team have discovered that stroke not only damages the brain but weakens the immune system and allows bacteria in the gut to escape and cause infection in other parts of the body.

The Fellowship will enable Connie to investigate how the brain communicates with the immune system as well as researching new strategies to restore the gut barrier’s integrity following stroke.

“I hope that in five years’ time I will have made a difference in how patients with stroke are treated, found new ways of stopping infection, and developed therapies to wake up the immune system without damaging effects,” said Dr Wong.

Dr Daniel Pellicci from the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, and Murdoch Children’s Research Institute wants to recruit specialist white blood cells, known as ‘unconventional T-cells’ in the fight against tuberculosis (TB).

‘Unconventional T-cells’ are among the immune system’s first responders. They can kill infected cells and recruit other parts of the immune system to destroy the attackers.  Until now, these cells have been difficult to study but Daniel has developed investigative tools to uncover the basic biology of how these cells work in the immune system.

Daniel will use his Fellowship to focus on people suffering from tuberculosis. He hopes his work will lead the way to an improved TB vaccine as well as other new immune therapies.

“In the longer term, I think we’ll be able to develop potent lipid molecules to stimulate these cells to help fight various infectious diseases, plus other diseases that involve the immune system such as cancer, autoimmunity and allergies,” said Dr Pellicci.

“Australian research has an excellent track record in new discoveries to address the world’s unmet medical needs,” said CSL Chief Scientific Officer Dr Andrew Cuthbertson.

“The CSL Centenary Fellowships acknowledge that reputation and aim to grow the quality and quantity of Australian biotech through well-funded, long-term support.”

“The Fellows are a group of exceptionally bright young Australians, each with decades of research ahead of them, and who will become some of Australia’s pre-eminent scientists. We look forward to following their careers as they in turn lead and mentor a new generation of promising medical researchers,” said Dr Cuthbertson.

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Media contact:Christina Hickie Christina.Hickie@csl.com.au, 03 9389 3425 / 0429 609 762

Photo & Interview opportunity: Dr Wong and Dr Pellicci will be presented with their CSL Centenary Fellows certificate at an award presentation in Melbourne on Thursday 11th October at an Arts Centre Venue. Media are invited to attend. For details, contact Christina Hickie: 0429 609 762

About the CSL Centenary Fellowships
The Fellowships are competitively selected, high value grants available to mid-career Australians who wish to continue a career in medical research in Australia. Two individual, five-year, AUD$1.25 million fellowships are awarded each calendar year. www.cslfellowships.com.au

About CSL

CSL (ASX:CSL) is a leading global biotechnology company with a dynamic portfolio of life-saving medicines, including those that treat haemophilia and immune deficiencies, as well as vaccines to prevent influenza. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL — including our two businesses, CSL Behring and Seqirus -  provides life-saving products to more than 60 countries and employs 22,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest.  www.csl.com

RESEARCH PROFILES

Why do people with stroke die from infections? Connie Wong—Monash University, Melbourne

Stroke is responsible for ten per cent of deaths worldwide. Up to a fifth of these deaths are from pneumonia and other infections following the stroke. Dr Connie Wong now knows why.

Connie and her team discovered that stroke not only damages the brain but weakens the immune system and allows bacteria in the gut to escape and cause infection in other parts of the body.

The $1.25 million CSL Centenary Fellowship will give Connie the opportunity to work out how and why the gut barrier breaks down after a stroke.

She’s also going to investigate how the brain communicates with the immune system; find new strategies to restore the gut barrier’s integrity; and test novel therapies to revive the immune system after a stroke so it can keep fighting infection.

“I’m very intrigued by the brain. I want to understand how a brain injury, such as a stroke, can change the way the body fights an infection.

“Clinicians will give patients antibiotics, but clinical trials have shown that antibiotics aren’t effective in reducing the rates of infection or improving patients’ survival after infection,” says Dr Wong.

In 2011, Connie and her colleagues discovered that after a stroke the brain can send signals to relax the immune system. This prevents inflammation from damaging the brain while it’s repairing itself – but it also stops immune cells fighting infections elsewhere in the body.

Then, in 2016, the team were the first to show that a stroke also changes the gut, making the gut barrier permeable. This allows bacteria to escape to other parts of the body, causing the killer infections. Now that Connie knows where the infections are coming from, she hopes to find ways to shut them down.

“You can get gap-filler for cracks in your house - we need something similar for the gut, like new drugs to seal up the gut barrier and stop the bacteria from escaping,” she says with a smile.

Connie also hopes her work will reduce the unnecessary use of antibiotics in the treatment of stroke.

“I hope that in five years’ time as a result of the CSL Centenary Fellowship I will have made a difference in how patients with stroke are treated, found new ways of stopping infection, and developed therapies to wake up the immune system again without damaging effects.”

Dr Connie Wong is a National Heart Foundation Future Leader Fellow at Monash University. Her research is supported by the National Heart Foundation and the National Health and Medical Research Council.

Further reading: research.monash.edu/en/persons/connie-wong

Unconventional T cells join the fight against TB Daniel Pellicci—The Peter Doherty Institute for Infection and Immunity & Murdoch Children’s Research Institute, Melbourne

Unconventional T cells are among our immune system’s first responders when infection strikes. They can kill infected cells and recruit other parts of the immune system to destroy the attackers. Dr Daniel Pellicci believes that these specialist white blood cells have huge untapped potential in the fight against tuberculosis (TB), cancer, allergies, autoimmune conditions and other diseases.

“The human immune system is amazing, but we’ve still got a lot to learn,” Daniel says. “My work is focussed on unconventional T cells, which are present in large quantities in humans and can rapidly mount a response to an invader, in minutes or hours, instead of the days or weeks required by some other parts of the immune system.”

Conventional T cells, work by recognising protein fragments from disease-causing pathogens but can trigger an unwanted immune response and cause the rejection of transplants or the development of autoimmune disease.

Unconventional T cells, by contrast, work by recognising fat or lipid molecules from pathogens, and this recognition process is identical from one person to another. They avoid the complications of their conventional counterparts.

Daniel will use his $1.25 million CSL Centenary Fellowship to investigate unconventional T cells in people suffering from tuberculosis. His team will investigate how these cells function in patients with latent or active TB, and in people who have been vaccinated against the disease.

The BCG vaccine—our current defence against TB—is effective at preventing infection in only about 20 per cent of children, and is even less effective in adults. Almost two billion people are infected with TB and it kills more than a million people each year. Daniel hopes his work will lead the way to an improved vaccine.

“Further, in the longer term I think we’ll be able to develop potent lipid molecules to stimulate unconventional T-cells to help fight multiple infectious diseases, plus other diseases that affect the immune system such as cancer, autoimmunity and allergies” he says.

Dr Daniel Pellicci is a Senior Research Fellow with the University of Melbourne and Peter Doherty Institute for Infection and Immunity, and next month will take up a group leader position at the Murdoch Children’s Research Institute. His research is supported by project grants from the NHMRC and he was recently awarded the 2018 Commonwealth Health Minister’s Medal for Excellence in Health and Medical Research and an NHMRC Research Excellence Award.

Further reading:pursuit.unimelb.edu.au/articles/tapping-into-the-power-of-unusual-white-blood-cells

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