Breakthrough April 2019 - issue 41

Targeting tuberculosis The key to better tuberculosis prevention – and to improving the odds for millions of patients globally – could lie in boosting the body’s natural levels of a small immune molecule called interferon gamma, our scientists have revealed. Together with an international team of researchers, Professor Stuart Tangye studied patients with rare genetic variants that left them more susceptible to developing tuberculosis than the general population. The scientists investigated the intricate mechanisms of the patients’ immune systems and discovered that they produced less of the immune molecule interferon gamma, which fends off bacterial and viral infections. This work could significantly change how scientists think about developing tuberculosis therapies in the future. Current treatments target the bacteria that cause the disease, but they have side effects and many patients become drug resistant. Treatments that boost the body’s natural production of interferon gamma could give those exposed to tuberculosis a better chance of avoiding the disease. NEW RESEARCH New clues from cancer DNA Our researchers have discovered a new pattern of chemical tags on DNA which reveals new insights into how cancer develops. A team led by Professor Susan Clark and Associate Professor Clare Stirzaker took a close-up view of the two meters of DNA wrapped up inside prostate cancer cells. They investigated 28 million chemical tags that can attach to DNA and change how the DNA is read. By comparing the pattern of DNA tags between prostate cancer and normal cells, the team discovered a surprising pattern which is common in different cancer cell types and which has never been seen before. This pattern revealed that specific molecules around which DNA wraps may provide a ‘seed’ for cancer to develop. The discovery is an important first step towards improving cancer therapy. By understanding the precise changes that take place when normal cells become cancerous, our researchers hope to uncover new ways to treat or even prevent cancer from developing. Read more at: garvan.org.au/tb-molecule

Welcome from our Executive Director

THROUGH THE MICROSCOPE

A close-up image of the immune system in action is giving Garvan researchers new insight into autoimmune disease.

Dear Garvan family,

It’s with a great sense of pride and enthusiasm that I greet you in our first Breakthrough of 2019.

In this issue, you will be introduced to the Australian Parkinson’s Mission, a collaborative program integrating clinical trials with genomics research for Parkinson’s. You will also learn about CIRCA, a team of doctors and researchers changing the lives of people with rare immune diseases, just like Oscar featured on page 8. Understanding the role of genomics, or our DNA, in health and disease is becoming more and more important. The expertise of the researchers here in genomics and cellular genomics – the genomics of single cells – is something I’m extremely proud of. On page 10, you’ll see an infographic that gives an overview of how we analyse the genomes of cells using the cutting-edge capability in our Garvan-Weizmann Centre for Cellular Genomics. Throughout 2019, we are hosting a series of free and informative tours and seminars to share exclusive updates about our research. I extend my warmest invitation to you, your family and friends, to join us, please register here: garvan.org.au/public-seminars. There are many exciting research breakthroughs, clinical trials and updates on collaborative programs to share with you, as well as inspiring stories of people like you, Garvan’s generous supporters, so please read on.

Pictured in this image in red is an immune cell called a macrophage - a ‘big eater’ that cleans up dying B cells, whose nuclei are shown here in blue.

With very best wishes,

‘Taking out the garbage’ is not just a household chore - your immune system works hard to remove waste each and every day. To better understand the body’s cleaning processes, our researcher Associate Professor Tri Phan is using advanced intravital two-photon microscopy to investigate immune cells in action.

Pictured in this image in red is an immune cell called a macrophage - a ‘big eater’ that cleans up dying B cells, whose nuclei are shown here in blue. These dying B cells, if not removed from lymph nodes, can trigger dangerous signals in the body that activate the onset of autoimmune conditions such as lupus. Understanding how these big eaters take out the B cell ‘garbage’ is a key first step to better understanding these chronic debilitating conditions - and ultimately to developing better treatments.

Professor Chris Goodnow FAA FRS Executive Director The Bill and Patricia Ritchie Foundation Chair

Read more at: garvan.org/immunology

Read more at: garvan.org.au/new-clues

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