Tom says

SVI’s focus throughout the current pandemic has been on maintaining essential long-term experiments and productivity so we do not lose vital experimental progress or results. 

Our researchers have been working in the labs throughout this period, some on COVID-19 related experiments, and others on their ongoing studies. Those of us not engaged in daily hands-on experimental work have been “busy” with endless Zoom meetings from home. 

We are conscious of the financial impact of COVID to SVI and to other similar organisations but with your help and government support we, at this stage, are hoping to avoid major impacts on our staff. Our Audit and Risk Committee, Board and Finance Team are monitoring the situation closely. 

We are also very conscious that the strain on our staff like on many others in the community is a serious issue. For young people, those with small children and for people living alone this is an especially tough time. SVI is concerned for our staff’s well-being and we are doing all we can to make coming to work, or working from home, both safe and manageable. 

Like others who are more expert than me, I am optimistic about the prospect for one or more vaccines and for new drugs to combat the virus, but these advances will take some time. It seems likely that cases in Victoria will fall to a low number in the coming weeks, but it may be hard to get all the way to zero. Therefore, as well as a focus on the post-COVID future, we need to learn to live with a persistent but low number of cases for the time being. 

This will be a big challenge for the health system and the whole community. SVI looks forward to helping our collaborators in St Vincent’s Hospital and other research institutes with this agenda, as well as continuing to work hard on our important non-COVID related research challenges. 

In a time when many of us are consumed with the bad news that we see in the media every day, I’m happy that we are able to share some really positive stories about our fantastic young researchers and the important work they are doing to help improve health outcomes for all of us. I hope you enjoy reading this issue of The Edman. 

Beating breast cancer with artificial intelligence

To the untrained eye, it is almost impossible to identify a potential cancer on a mammogram. 

A mammographic image shows breast tissue in variations of grey and white on a black background. Generally speaking, the denser the tissue, the whiter it appears. White areas on a mammogram may reveal normal tissue and glands, areas of benign breast changes or potential problems, such as a cancer. And no two breasts are the same. 

This is what radiologists have to take into account when ‘reading’ an image, and is why each mammogram that is performed is analysed by two experts. If the experts disagree, then a third arbitrates. 

While this screening is credited with saving countless lives, there is room for improvement. 

A multi-disciplinary group led by St Vincent’s Hospital Melbourne and SVI has been awarded a $2.26 million grant from the Australian Government’s Medical Research Future Fund (MRFF) to apply Artificial Intelligence to improve mammographic screening outcomes. 

A key component of the project is a series of studies where researchers will use an Artificial Intelligence algorithm that they have trained to detect breast cancer in mammographic images. 

The algorithm will be tested alongside scans that are done each day at St Vincent’s Hospital Melbourne, home to the state’s largest BreastScreen Victoria clinic. 

Project lead, Dr Helen Frazer, Clinical Director at St Vincent’s Hospital Melbourne’s BreastScreen, says the project represents a unique opportunity to play a leading role in Australia’s battle against breast cancer. 

“Breast cancer is the most common cancer affecting Australian women,” says Helen. 

“More women are recalled to assessment after a mammogram than those who end up with an eventual cancer diagnosis. By using Artificial Intelligence screening models alongside our existing practices, we hope to transform Australia’s breast screening program and reduce the number of lives lost to breast cancer.” 

Holyoake Research Fellow, Dr Davis McCarthy, is a computational biologist who works with large and complex data sets to explore and solve major health problems. He is SVI’s lead researcher on the project, and says that breast screen data is ideal for Artificial Intelligence development. 

“Working with BreastScreen Victoria allows us to draw on 20 years of high-quality data to inform our algorithm. At the heart of our study is a desire to help Australian women – designed using machines and images that are relevant to the Australian setting.” 

The 3-year research project also involves partners at The University of Melbourne and The University of Adelaide. 

Davis’ research is carried out through a joint appointment with the University of Melbourne and is generously supported through philanthropy, via a donation from former SVI Board member Paul Holyoake and his wife, Marg Downey. 

How to mend a broken heart

Imagine being told as a teenager that you have a degenerative disease which will cause loss of muscle co-ordination, fatigue, vision impairment, hearing loss, slurred speech and then a serious heart condition. 

Friedreich’s Ataxia is a hereditary neurodegenerative disorder that affects one in 30,000 Australians. It is most commonly diagnosed between the ages of 5 and 18 and it quickly and ruthlessly robs those diagnosed of their mobility. There is currently no cure.

Postdoctoral Fellow Jarmon Lees, from SVI’s OBI Department, has recently been awarded a Friedreich’s Ataxia Research Alliance (FARA) Postdoctoral Award to investigate the causes of heart disease in people with Friedreich’s Ataxia.

“The main cause of premature death in people with the condition is heart failure, but it is unclear exactly what the disease does to the heart,” says Jarmon. 

Jarmon says that one of the hurdles to understand how and why heart problems occur in Friedreich’s Ataxia is that there has been no way to mimic the heart of someone with the disorder using animals or cell models in the lab. Developing such a model has been a particular challenge because the heart is a complex organ made up of a mix of different cells, including heart muscle and blood vessel cells, but also nerve cells that control heart rate and rhythm.

To overcome this, Jarmon and his supervisor Dr Shiang (Max) Lim, have developed a way to ‘grow’ a heart in the lab, using adult cells that have been donated by people with the disease. The pair will use these ‘hearts in a dish’ to understand exactly why people with the disorder develop heart problems. 

“We develop in the womb from a stem cell. We now have ways to ‘wind the clock back’ by turning cells from an adult back into stem cells. We can then apply different conditions to coax these stem cells to form all the different cells which make up the heart,” says Jarmon.

After making the different cell types, the researchers combine the cells together in a dish in the incubator in the lab. After as little as a week, an organoid forms that beats rhythmically at a rate that resembles a foetal heartbeat.

Over the next 2 years, Jarmon will use these organoids to unravel the causes of heart disease in Friedreich’s Ataxia. 

“These ‘hearts in a dish’ will also allow us to test drugs that might be used to treat the condition,” says Jarmon.

In this way, the team ultimately aims to provide new hope to young people diagnosed with the disease.

This research is funded by FARA (Friedrich’s Ataxia Research Alliance) and Friedreich Ataxia Research Association (fara Australia).

A positive life

Being diagnosed with a degenerative muscle disease that can lead to a serious heart condition would stop many people in their tracks.

But Leah has spent the two decades since receiving her diagnosis of Friedrich’s Ataxia living a full and busy life.

“I was 17 and I began to feel unsteady on my feet, particularly when going downstairs,” says Leah. “I also felt uncoordinated when running and playing sport, something which I had always been quite good at.”

“After I was diagnosed, I remember reading what could happen in the future, and I thought ‘No way! This can’t happen to me!’”

Leah’s family was upset, but kept reassuring her that everything would be okay. 

“A doctor had said at my time of diagnosis that I only had ‘mild’ symptoms. My family have held onto this word and still refer to this today. I think it makes them feel better. I know that my dad feels a lot of guilt and blame. However, it’s no one’s fault.”

From the day she was diagnosed, Leah has done what she can to keep her symptoms at bay. 

“Working out at the gym, physio, hydrotherapy, chiropractic, osteopathy, speech therapy, massage treatments … you name it, I do it. Learning mental strategies to help cope with a diagnosis like Friedreich’s Ataxia has allowed me to live a positive life.”

A big driver for Leah’s commitment to doing whatever she can to cope with her condition, is her two young children. “My dream is to be able to walk, unaided, alongside them one day and to dance with my son on his wedding day.”

Leah has a soft spot in her heart for medical researchers and has a message for them: “Firstly, thank you. Thank you for doing what you do and trying to help others. You’re all angels.”

Not content to be an observer, she participates in any drug trial or research study that she can and has found them all to be a positive experience. “The main thing is – they provide hope!” 

And when it comes to the donors who give gifts – of any size – to support SVI research, Leah cites a favourite quote, “Do not underestimate a moment of your kindness. It has the power to change lives in ways that you may never know.”

About Friedrich's Ataxia

• Friedreich’s Ataxia is a debilitating, life shortening degenerative neuro-muscular disorder. 
• It affects about 1 in 30,000 people in Australia and New Zealand. 
• It is most commonly diagnosed between the ages of 5 and 18 years. 
• It leads to loss of muscle co-ordination, fatigue, vision impairment, hearing loss and slurred speech, scoliosis (curvature of the spine), diabetes and serious heart conditions. 
• It is caused by an inherited genetic mutation that limits the production of a protein called frataxin. 
• Without enough frataxin cells do not function properly, which can result in debilitating medical problems, particularly of the nerves and heart. 
• Although there has been significant progress towards treatments, there is currently no cure.

Information sourced from the Friedreich Ataxia Research Association Australia website.

A medal for Winnie

Former SVI PhD student Winnie Tan has been awarded the 2020 TJ Martin Medal. Named in honour of former SVI Director, Professor Jack Martin, the medal is awarded annually for the best MD or PhD student thesis from the St Vincent’s campus submitted in the preceding year. 

Winnie did her PhD in SVI’s Genome Stability Unit under the supervision of Associate Professor Andrew Deans.

During her PhD, Winnie showed the means by which a protein called FANCD2 protects cells from developing mutations that might be cancerous, solving a 20-year mystery along the way. 

It had been long known that FANCD2 was a key part of the vast and intertangled protein network that the cell uses to repair DNA damage, but its exact role was unclear.

Winnie showed that FANCD2 physically coated the length of DNA when it had been damaged, protecting it from further damage and helping to activate DNA repair processes.

Her findings have implications for understanding how cancer develops and are particularly relevant to a disease called Fanconi Anaemia, which can be caused by mutations in the FANCD2 protein, and is a focus of research in the lab. 

The results form the basis of Winnie’s PhD thesis, which was passed in February. The newly minted doctor intends to remain in the lab at SVI, in order to bring her findings closer to helping people with Fanconi Anaemia.

Donors help build bridges

We spoke to long-time Institute supporter Dene Buxton about what compels her family to give to medical research. 

“Over the past few years, our Family Foundation has been involved in the wonderful SVI Rising Stars Program, offering support to our young clinician-researchers, allowing them to concentrate on their research rather than writing submissions for grants,” Dene says. 

“These extremely talented women and men need our assistance more than ever. As the world desperately searches for medical breakthroughs, the answers lie in research.”

Clinician-researchers are trained in both science and medicine, with post-graduate research qualifications in addition to their medical degree. They are motivated by a wish to improve disease outcomes by understanding the mechanisms that underlie disease, or that drive response to treatment in their patients.

One such researcher is Anna Galligan, an endocrinologist and Masters student who works under the supervision of Dr Bala Krishnamurthy and Professor Tom Kay, in SVI’s Immunology Laboratory.

Anna’s research project, which is generously supported by the Buxton family, focuses on the effects of one of the great hopes for cancer treatment – immunotherapy – which works by mobilising the body’s own immune system to recognise and eradicate cancer cells.

“My interest in autoimmune diseases and, in particular, type 1 diabetes, led me to the team at SVI,” says Anna. “As an endocrinologist, I was deeply concerned that some cancer patients who undergo immunotherapy treatment suddenly develop autoimmune diseases, including type 1 diabetes and thyroid disease,” says Anna. 

“In addition, people with autoimmune disease have been excluded from some of the clinical trials of immunotherapy because of concerns that the treatment might activate their already overactive immune system.”

“It is clear that we need to know more about how immunotherapy interacts with the body’s immune system.”

Anna’s project aims to find ways to predict who might be predisposed to develop an autoimmune disease during immunotherapy treatment. They hope this work will eventually allow cancer patients to be treated more effectively, without risking development, or exacerbation, of an autoimmune disease.

By providing an essential bridge between the laboratory and clinical practice, and aided by philanthropy, Anna hopes to ultimately provide her patients with better health outcomes.

“I’m so grateful for the philanthropic support provided by Dene and Andrew Buxton,” says Anna. “When others believe in you so strongly, you can’t help but be motivated to succeed.” 

“I’m looking forward to building a career that bridges both clinical medicine and research when I complete my degree this month. The Buxtons, and SVI, will have played a major part in helping me realise that dream.”

“We’ve been thrilled to assist Anna in her research program focusing on the effects of immunotherapy as a way of treating cancer and wish her all the best in her career,” says Dene. 

“We’d also like to thank SVI for the opportunity to see first-hand the effort and dedication of these amazing young researchers who are our future!”

Image: Dene Buxton and fellow SVI supporter Simone Carson AM

Young scientists reach for the stars

Thanks to generous contributions of our supporters at SVI’s 2020 For the Love of Science Dinner, we were able to provide four of SVI’s brightest emerging researchers with Rising Star Awards to help fund their research projects. 

Dr Natalie Wee, EH Flack Fellow, Bone Cell Biology and Disease Unit 

“When an elderly person breaks a bone, the consequences can be devastating.

Osteoporosis affects over 1 million Australians. It weakens the skeleton, increasing the risk of fractures, particularly to the hip, spine, and wrist. 

Too often these injuries are the trigger for ongoing health issues that have huge personal and social costs. Alarmingly, people who suffer a fragility fracture, particularly to the hip, are at higher risk of dying, with death rates of up to 24% in the first year after the break.

Current therapies can preserve bone strength in the spine, but they don’t work on other areas, such as the femur, hip or wrist – the sites that need strength the most when someone falls. 

My research aims to understand the signals that control bone strength and then use this knowledge to find new treatments for osteoporosis.”

Dr Ash Hoque, Metabolic Signalling Laboratory

“An enzyme called AMPK is thought to hold the key to many of the most common diseases affecting our society, including cancer, type 2 diabetes, and neurodegeneration.

AMPK controls the ability of cells to match growth rate with the availability of energy and nutrients – a key requirement for all living organisms. By doing so, it functions as the ‘fuel gauge’ of the cell, speeding up cell growth when nutrients are abundant and slowing cell growth when nutrients are scarce.

Even though we’ve known about AMPK for many decades now, we only have a very basic understanding of how it is controlled. Learning more about this will allow us to exploit its potential as a target for new treatment strategies.” 

Dr Chris Langendorf, Protein Chemistry and Metabolism Unit

“Australia has the fastest growth rate of adult obesity in the world, significantly increasing our risk of devastating conditions including type 2 diabetes, cardiovascular disease and cancer.

The cost is not just personal – the increase in obesity-related disease places a mounting financial burden on the Australian economy and a physical strain on the healthcare network.

We already know that high fat diets disrupt normal biochemical processes, leading to increases in fatty acid metabolites – substances made or used when the body breaks down food.

But to tackle the problem, we need to understand more about how fat affects the body at a molecular level. This is what I seek to understand.”

Dr Pushpak Bhattacharjee, Human Immunology Laboratory

“Around 140,000 Australians live with type 1 diabetes. Six new cases are diagnosed every day. Unable to produce the insulin needed to turn sugars from food into energy, people with type 1 diabetes rely on insulin injections to regulate their blood sugar.

The condition is hard to control and can lead to devastating consequences, including cardiovascular disease, kidney and eye problems, and even premature death.

We know that type 1 diabetes develops when misguided cells from the body’s own immune system destroy the beta cells that produce insulin in the pancreas. 

My aim is to identify the triggers for the autoimmune response and use this knowledge to develop new therapies.”

SVI Foundation Board Chair, Karen Inge, is grateful for the support shown by SVI’s donors to the Rising Star Program.

“Our Rising Stars are passionate and ambitious and are the driving forces for novel discoveries with the potential to impact health.“

Sign up and tune in

Thanks to those who joined us for our recent Food Matters webinar series.

The series was kicked off by Professor Natalie Sims, who spoke about the cause, prevention and treatment of osteoporosis. The second seminar was presented by Dr Ramin Shayan, who spoke about the connection between nutrition and cancer.

The last webinar will be presented on Thursday 17 September by SVI Director Professor Tom Kay, who will talk about an upcoming type 1 diabetes clinical trial and the impact this research can have on those in the early stages of the disease.

Each webinar presentation is followed by a short nutritional talk by Accredited Practising Dietitian, and SVI Foundation Chair, Karen Inge.

These are free online events, however bookings are necessary. Once you register, a Zoom link will be emailed to you on the day of the event, with details on how to join the webinar.

If you can’t join the webinar on the day, a video recording will be sent post event so you can watch in your own time. 

For enquiries, please email Nicola Peniguel at [email protected].

Deputy Director receives international award

SVI Deputy Director Professor Natalie Sims has been awarded the prestigious Paula Stern Achievement Award by The American Society for Bone and Mineral Research (ASBMR).

The Award annually recognises a woman in the bone field who has made significant scientific achievements and who has promoted the professional development and advancement of women in the field.

“This Award recognises the significance and impact of Natalie’s body of research and her commitment to forging career paths for female scientists,” says SVI Director Tom Kay. 

“Her ability to engage with people of all backgrounds and expertise has proven to be a great asset for not only SVI, but the scientific community as a whole. This Award is a wonderful acknowledgement of Natalie’s 30-year career as both a researcher, and a mentor, and is well-deserved.” 

Natalie is internationally recognised as a leader of bone research. For the last 30 years she has worked to discover new treatments for common skeletal conditions such as osteoporosis and arthritis, as well as rarer disorders, like osteogenesis imperfecta, that affect the way the skeleton is formed. 

Natalie is President of the Australia and New Zealand Bone and Mineral Society and holds senior editorial positions for a number of scientific journals. Her team investigates the way that cells within the skeleton communicate with each other to produce bone of optimal shape and strength.

Natalie has helped many young Rising Stars establish their careers in medical research.