Melbourne is one of the great medical cities of the world. There is no doubt that the scale and quality of the academic and clinical components of Melbourne medicine are second to very few, even if governments would prefer more industry focus and the generation of more wealth.
The sector has an impressive capacity with two genuinely world-class medical schools and a remarkable collection of medical research institutes (including SVI) that support strong teaching hospitals.
Enough of the hubris and boasting – what of it? First, for all of us in the community this is a huge advantage when we need medical care, which undoubtedly most of us will at some stage. It is no wonder Australia has a high life expectancy and our health care is highly regarded. Second, we should think about what can be done to make it even better – realistically, could we collectively be the best in the world?
One of the ways forward is to knit our quite fragmented system together so that the organisations work as one large enterprise, or at least as much larger parts than they have in the past. This should ensure collaboration on projects and back-office efficiency.
SVI is involved in many such initiatives. The Aikenhead Centre for Medical Discovery (ACMD) on the St Vincent’s campus is one. ACMD is a collaboration between the Hospital, five universities and three research institutes, and also has a developing relationship with CSIRO. It has been an exciting year for those involved in the project, with announcement of funding from the Federal and State Government that will enable the new building to proceed on the corner of Nicholson St and Victoria Parade. Completion is planned by the end of 2024.
Another example of more recent collaboration is the Victorian Comprehensive Cancer Centre – a state-wide collaboration between hospitals and research institutions that are active in cancer research and care. SVI’s cancer researchers are active participants in, and contributors to, these activities.
The Melbourne Academic Centre for Health, which includes many hospitals and research institutes affiliated with the University of Melbourne, has been designed to bring together and coordinate the activities of hospitals, research institutes and universities. These organisations have different, but related, goals and missions. There is a similar group, Monash Partners, for Monash-affiliated institutions.
We are also a member of the St Vincent’s Health Australia family, which seeks to realise the benefits of being a national organisation. Along with SVI in Melbourne, SVHA also includes the Garvan and the Victor Chang Cardiac Research Institutes in Sydney.
We are proud to be part of all these initiatives. There are many challenges in working across institutions and cohesion requires strong direction from the top. The opportunities are great if we can recognise that the real competition is outside Australia, not within, and that we will be stronger together than separately.
Finally, on a bittersweet note I want to take this opportunity to acknowledge the contribution made by Dr Anne Thorburn, our Head of Operations, who has stepped down after more than 17 years at SVI. Anne joined SVI after a highly successful career in nutrition and obesity research with Professor Joe Proietto at the University of Melbourne. Over her time at SVI, she has contributed tremendously. This was initially through her instrumental involvement in our Islet Transplantation Program back in 2002. More recently she played a key role leading and guiding the facilities and scientific operations of SVI – activities that are essential for our scientists to do their work. Anne has done a superb job and we wish her well in her next endeavours.
Breaking bad: secrets of bone strength discovered
Professor Natalie Sims says that about 60% of bone fractures happen in people who have had a normal bone density scan.
“Osteoporosis is becoming more common as our population ages. However, the standard test used to diagnose it – a bone mineral density scan – is not a great predictor of whether someone will break a bone.”
Natalie believes that better ways to predict and treat osteoporosis will come from improved understanding of the factors that control bone strength.
Recent work from Natalie’s lab, published in the journal Nature Communications in August, shows that cells within the bone, called osteocytes, play an important role.
Natalie explains that osteocytes have been overlooked for a long time.
“Osteocytes are found buried within the hard bone tissue. This makes them difficult to study and historically they were considered inactive and uninteresting. However, recent research, both from our lab and others, has shown that they are amazingly important.”
Natalie says that the long branch-like fingers of osteocytes reach through the structure of the bone itself and act as a sort of control centre. They regulate calcium levels in the blood, sense mechanical strain and help to control bone tissue renewal.
The recent work used sophisticated techniques developed in collaboration with the Australian Synchrotron that allowed the researchers to peer into the make-up of the bone itself. They did this in both normal mice and in mice in which a specific set of signals within the osteocytes has been disrupted. The team’s data showed that when these signals weren’t able to transmit properly, bone was more brittle and prone to fracture.
“We showed that the bones from our mice had a different pattern of mineralization and that it was the osteocytes that controlled this; not by changing the shape of bone, but by changing how much mineral was in the bone itself,” Natalie says.
“In human disease, it has been very difficult to work out why people with normal bone density scans get fractures. This work suggests it could be because their bone mineralises differently.”
This points a way forward to being able to diagnose and treat bone diseases like osteoporosis – by targeting the overlooked osteocytes it might be possible to improve the strength of the bone around them.
About the study
This study was supported by the National Health and Medical Research Council, the Australian and New Zealand Bone and Mineral Society and by a Brockhoff Foundation Early Career Grant to Dr Christina Vrahnas. The work was carried out in collaboration with researchers from Griffith University, The Walter and Eliza Hall Institute of Medical Research, Okayama University, the Australian Synchrotron, the University of Bordeaux and the University of Melbourne.
The cells in our body undergo constant division throughout our lives. The structures found at the ends of a cell’s chromosomes, called telomeres, shorten each time the cell divides. This acts as a sort of expiry date sticker for the cell, with death being triggered when the telomeres get too short.
Cancer cells have different strategies that allow them to circumvent this ‘expiry date’. One of these is known as “alternative lengthening of telomeres”, or ALT.
Two studies undertaken in Associate Professor Andrew Deans’ Genome Stability Unit, have highlighted a mechanism that might eventually allow us to specifically kill cancer cells that rely on the ALT mechanism.
Dr Julienne O’Rourke, who recently completed her PhD in SVI’s Genome Stability Unit, co-authored one of the studies. She says that there are currently no specific therapies for cancers that are ALT-positive.
“This type of cancer is resistant to treatment. About 40% of soft-tissue cancers including osteosarcoma (bone cancer), liposarcoma (a cancer originating in fat cells), and angiosarcoma (blood vessel cancer), as well as 10% of other cancer types, such as breast, ovarian and prostate, are ALT-positive.”
The studies show that a protein called FANCM, which was the focus of Julienne’s PhD, is needed in order for an ALT-positive cancer cell to survive.
The researchers showed that they could kill ALT-positive cancer by reducing the amount of FANCM in the cells. Particular excitement stems from their finding that reducing the amount of FANCM specifically targets the ALT cells, without affecting healthy cells. This makes FANCM a promising target for new drugs to kill cancer cells that use the ALT strategy to survive.
“We’re all excited by the life-changing and life-saving potential for children and other people with these cancers; it’s not every day you make discoveries that could lead to treatments that could save lives,” says Andrew.
About the study
This work was carried out in collaboration with the laboratory of Associate Professor Hilda Pickett at Children’s Medical Research Institute in Sydney, and with Professor Claus Azzalin’s lab in Lisbon, Portugal. Funding for the research was provided by Cancer Council Victoria, Cancer Council NSW and the National Breast Cancer Foundation.
Chemo mystery solved
Jim Wilson’s son Sam died of neuroblastoma when he was just 6 years old.
“I know I speak for many when I say that a cancer diagnosis is devastating, but it is particularly hard for young children and their families to navigate. Providing cancer patients with the tools to battle cancer can give both relief, and hope,” says Jim.
He knows that new treatments do not emerge without the underpinnings of fundamental knowledge — without first answering a range of complex biological questions of the sort being asked by researchers at SVI.
SVI scientists are part of an international team that recently published their work showing how cancer cells bypass the effectiveness of a commonly used cancer drug, called cisplatin.
The finding has the potential to lead to more effective treatments for a number of cancers including neuroblastoma, which most commonly occurs in infants and young children.
“Cisplatin is quite successful against a range of cancer types,” says Professor Michael Parker, Head of SVI’s Structural Biology Unit and one of the study’s authors.
“However, many people experience side effects from the drug, and most patients eventually develop resistance to it: our work aimed to understand why this was the case.”
Michael explains that cisplatin works by binding to a cell’s DNA and creating blockages that interfere with its ability to divide. This causes cancer cells, which divide faster than normal cells, to die.
The team identified an enzyme found in the cell, called GST P1-1, that renders the cisplatin drug ineffective.
“GST enzymes are found in every cell of the body; they are ‘good guys’ that protect us from toxic molecules which come from a variety of sources including the food we eat, smoking and exposure to UV radiation. The enzymes attack toxic molecules which are then pumped out of the cell,” says Michael.
“Using a technique that helps us to determine the molecular structure of proteins, called X-ray crystallography, we were able to show that cisplatin and GST P1-1 bound to each other.”
Michael says that this attachment causes the GST enzyme to act like a sponge, soaking up and storing cisplatin, thereby stopping its anti-cancer activity.
“We are now looking at designing new drugs that will prevent the GST P1-1 enzymes from attaching to cisplatin, so that this type of resistance is interrupted.”
Jim Wilson says, “If this research leads to a new drug that is able to reduce the side effects of cisplatin and allow it to continue its work to destroy cancer cells, then in my eyes that’s a real game changer.”
About the study
The work was supported by an Australian Research Council (ARC) project grant with major equipment support from the Australian Cancer Research Foundation. Other support included a National Health and Medical Research Council of Australia (NHMRC) Dora Lush Scholarship and an International Centre for Diffraction Data Crystallography Scholarship; provided to Dr Lorien Parker.
The article was published in the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).
Nurturing the future
A cornerstone of SVI’s success is the ability to attract excellent researchers and outstanding students.
A case in point is PhD student Wilson Castillo-Tandazo, who trained as a physician in his native Ecuador, before coming to SVI.
Wilson’s supervisor is Associate Professor Carl Walkley from the Cancer & RNA Biology Lab. Wilson’s research is focused on Rothmund-Thomson Syndrome; a rare genetic condition that manifests in infancy and leads to a wide range of medical issues, including an increased chance of getting cancer.
Wilson says, “There are two reasons why I chose to do my PhD at SVI. First of all, I wanted to work with Carl. And second, I wanted to work at an Institute that has different areas of research. At this stage of my career, it is very important for me to learn as many techniques and concepts as possible from different fields to build up the skills that I will require for my career.”
Wilson’s hard work is paying off; he just had his first research paper based on his PhD project published. He was also awarded 2018 International Student of the Year (Research) in the Victorian International Education Awards and is the recipient of a top-up scholarship funded through the SVI Support Group.
Wilson’s long-term goal is to improve the treatment and out-comes for children with cancer.
“The mechanisms behind Rothmund Thomson Syndrome are poorly understood, and an effective treatment is practically non-existent, which leads to very low survival rates. Through my research, I endeavour to contribute to the understanding of the disease, and eventually, to the development of new treatment options, which will have a direct impact on patients.”
By training talented and creative young researchers like Wilson, SVI, with help from our generous supporters, is nurturing the future of medical research.
Louise Purton appointed Professor
Louise Purton, Head of SVI’s Stem Cell Regulation Laboratory, has been appointed an honorary Professor by the University of Melbourne.
“Louise’s contribution to our understanding of how the body regulates its production of blood cells and how this can go wrong is internationally acknowledged,” SVI Director, Professor Tom Kay said. “We are extremely proud to see her recognised by the University with this appointment.”
Louise has pioneered studies showing that vitamin A is a key regulator of blood-forming stem cells and also the microenviron-ment in which they are made.
Louise says, “I love solving puzzles and research is an ongoing puzzle. You always have questions and the only way to find the answer is to figure it out yourself. My goal is to translate my answers into clinical solutions to improve patient outcomes for people with blood diseases.”
Louise’s research has to date resulted in numerous grants, peer reviewed articles and four clinical trials.
Louise is also passionate about fostering career development, with a focus on women in science, technology, engineering, mathematics and medicine (STEMM).
Focus on families
In June, SVI hosted the second Fanconi Anaemia (FA) Family Day.
The event was founded by SVI researcher Dr Wayne Crismani, who was inspired by the passion of people with Fanconi Anaemia and their families to learn about current research and advances in the fight against the disease. The day provides an opportunity for families affected by the disease to meet each other, share their stories and hear about current research from scientists all over the world.
Fanconi Anaemia is a rare genetic condition that typically leads to loss of normal blood production (including aplastic anemia and acute myeloid leukemia), often in early childhood. Even after a life-saving bone marrow transplant, people with the condition are left with a predisposition to cancer many hundreds of times higher than the general population. SVI’s Genome Stability Unit is the only research group in Australia that has a team dedicated to unlocking the mysteries of the disease.
Wayne says, “The success of the event is completely dependent on the families from New Zealand and Australia who make the effort to come together for the meeting. This provides us with the opportunity to learn from them about how we can better partner together to connect patients to appropriate medical expertise, which in turn can inform our research programs.”
The people who attended the day were excited to hear about the cutting edge research that is occurring in Australia and to have the opportunity to improve the resources available to fight the disease.
One participant said, “Research often is an abstract matter where practical application is not immediately visible. SVI and their researchers have shown that they’re so much more than biology and chemistry. The patients and families are at the heart of what they do. They care.”
We would like to thank all families for their enthusiasm and generosity in sharing their stories, and all of the speakers who took the time to share their unique insights and expertise through presentations, ‘fireside chats’ and Q&A sessions.
Maddie Riewoldt’s Vision is SVI’s major partner and funder for research into bone marrow failure syndromes and is supporting research into the development of urgently needed treatments for Fanconi Anaemia and other related conditions. Other supporters for the day included Melbourne Museum, BMG Labtech and Perkin Elmer.
The pregnant pause
Type 1 diabetes researcher Dr Michaela Waibel took maternity leave in 2018 following the birth of her first child, Nina.
“Five months after Nina’s birth, I was given the opportunity to start working from home one day a week to support our type 1 diabetes research program remotely. This enabled me to stay actively involved in our research projects and their progress. After my period of maternity leave, I returned to the Institute part-time in early 2019.
Our laboratory focuses on finding better treatments for type 1 diabetes. We have been working with a new class of drugs called JAK inhibitors, which are showing very promising results in both early prevention and reversal of type 1 diabetes, and in islet transplantation.
Our work using JAK inhibitors to stop or slow down the progression of type 1 diabetes has now progressed to the stage of setting up a clinical trial. This is the closest I’ve been to clinical translation as a researcher.
It is very exciting to be involved in the work in the lab, which is so close to improving outcomes for people with type 1 diabetes.
During my maternity leave, support from the Susan Alberti Women in Research Award funded a research assistant to continue my work in the lab.
Nina is now almost 18 months old, and keeps me on my toes. While she can be pretty demanding, I think I’ve finally found the right balance.”