This April marked the 60th anniversary of the opening of the research laboratories at SVI. When we take people through the Institute today, we always begin by highlighting the contribution that was made by Jack Holt, our founding benefactor, and by Pehr Edman, our inaugural Director.
The vision of both Holt and Edman for the Institute in its early days is echoed today with our focus on excellent funda-mental biomedical research that has a clear line of sight to improved health outcomes. The medical research institutes in Melbourne, of which we are the third oldest, and with which we have close links both culturally and collaboratively, have an undeniable impact on Victoria’s economy, health outcomes and reputation as an international hub of discovery.
The last 12 months have been a successful period for SVI in terms of grant funding. It has also been notable for increased funding from philanthropy, industry and commercial sources. This has been driven by a sharper focus on sustainability of funding at the Institute. Sourcing funding from outside the traditional government grants insulates us from the vagaries of the grant system, and also helps us to achieve our goal of delivering impact through research excellence and its translation.
Our researchers have done well in a competitive environment, but the difficulty of obtaining grants and the increasing cost of the sophisticated technologies that support world-leading research highlights the role that philanthropy and other sources of funding play. SVI’s researchers have always been at the heart of our success and in this issue of The Edman you can read about some of our ‘rising stars’ who, supported by the SVI community, are leading the way with their research.
The heart of philanthropy
Dr Kim Loh, from SVI’s Protein Chemistry and Metabolism Unit has been awarded a $125,000 grant by the L.E.W. Carty Charitable Fund to further his work into understanding what causes cholesterol to build up in the arteries, resulting in heart disease.
On average, 23 Australians die every day from a heart attack, making heart disease the leading cause of death in Australian adults. The problem is mainly caused by the build-up of cholesterol within the walls of important blood vessels throughout the body. Left untreated, this can lead to heart attack, stroke, or heart failure.
Kim says that a large body of evidence suggests that specialised immune cells called macrophages are major contributors to the development of plaque build-up and associated heart disease due to accumulation of high levels of cholesterol within the cells.
His work aims to understand the cause of this accumulation in order to develop more effective therapeutic approaches for heart disease.
With the support from the L.E.W. Carty Fund, Kim will study a regulatory enzyme found within the cell, called AMP-activated kinase (AMPK). He will investigate how it controls cholesterol production in macrophages and will modify its activity, using drugs that have been developed in the laboratory at SVI, to see whether he can augment the body’s natural control mechanisms and reduce the development of arterial plaques.
The L.E.W. Carty Charitable Fund was established under the Will of the late Olive Muriel Carty, who died on 26 February 1977, to honour the memory of her late husband Leslie Ernest William Carty.
As both Olive and Leslie Carty died from heart-related conditions, it is fitting that, on the 40th anniversary of the establishment of the Fund, Olive Carty’s far-sighted generosity will support Kim’s research into reducing the burden of heart disease on the Australian community.
Unravelling the mysteries of DNA
Our DNA is constantly changing – during the course of evolution, genes have been created, mutated, duplicated and even lost. And while it is this ability to modify our DNA that lies at the very heart of our existence, our cells have also developed sophisticated mechanisms to protect DNA from changes that might cause problems.
SVI’s Dr Andrew Deans has based his career around understanding this tension between stability and variability in our DNA. He believes that knowledge of these processes will help us to understand the underlying basis of cancer and develop new ways of treating the disease.
In 2017, Andrew and his colleagues, SVI’s Associate Professor Jörg Heierhorst and Dr Wojciech Niedzwiedz from the Institute of Cancer Research in the UK, were awarded a 4-year NHMRC Project Grant to examine in detail one of the mechanisms by which the cell protects its DNA from mutation.
The grant focuses on the role of a protein called FANCM. Recently, it was shown that people with mutations in FANCM were predisposed to early-onset cancer, including head and neck cancers, leukaemia and breast cancer.
Andrew says, “We have shown that this protein – FANCM – plays a role in stopping the accumulation of what is called an R-loop: an area where the DNA double helix has been disrupted and exposed to damage.”
Andrew compares it to a knitted scarf in which a loop of wool is sticking out. If the loop is not pulled back into the knit, it is more likely to become frayed or ripped.
FANCM recognises that there has been a mistake and goes to the site of the problem, pulls and pushes on the loop to bring it back into place, and restores the integrity of the knit so that the whole scarf doesn’t unravel.
In the work funded by the NHMRC, Andrew and his team plan to examine the way that FANCM works in detail.
They will look at the proteins that partner up with FANCM to remove the loop and determine the consequences of disabling FANCM. They will also look closely at the relationship between FANCM mutation and breast cancer development.
“Our work will uncover how FANCM suppresses cancer, and how it plays a major role in response to several important chemotherapy drugs in cancer treatment. Importantly, this will tell us why particular FANCM mutations predispose to cancer and help us improve the use of these chemotherapies.”
Image: Chromosomes from a single cell, coloured with blue dye. The telomeres at the ends of the DNA are labelled in red and the centromeres, where the DNA is held together, are labelled in green
Banking on a cure
Endocrinologist and PhD student Michelle So has spent the last 3 years of her life doing the medical research equivalent of a ‘Where’s Wally?’ puzzle, with a layer of added difficulty. She has been trying to identify a specific type of immune T cell – her version of Wally – without knowing exactly what it looks like.
Her PhD project aimed at ident-ifying immune cells in the blood-stream in people with type 1 diabetes, specifically targeting those cells that are on their way to the pancreas with the task of killing insulin-producing beta cells.
Michelle says that if they were able to biopsy the pancreas of a person newly diagnosed with the disease, the job would be considerably easier.
“It would be like organizing to meet Wally and knowing that he is going to be standing at a certain spot at a certain time, wearing his striped red top and beanie. But as we can’t do a biopsy, what we are trying to do is find these cells in the blood-stream. That is a bit like trying to find Wally by turning up at a place far from where he was last spotted, without a good description of what he might look like.”
Michelle’s work wouldn’t have been possible without the assistance of the people who have donated to SVI’s Living Biobank. These people agree to provide a sample of blood on demand. This has the advantage of providing fresh, rather than frozen, blood cells – which is necessary for the delicate cells that Michelle is trying to find.
Using these samples, Michelle was able to show that immune cells in the blood from people who had recently been diagnosed with type 1 diabetes responded to a particular protein sequence that hadn’t been studied before. This indicates that the sequence, which is part of the precursor to insulin, may play a role in triggering the immune cells to attack, or in amplifying the immune response in people with the disease.
The team at SVI are now working towards a blood test which can identify people at risk of developing type 1 diabetes. This test will be used to measure if therapies to prevent the condition are working as hoped, which will enable new therapies to be evaluated rapidly.
Once she has submitted her PhD, Michelle plans to continue her training in the USA. “We now know much more about what these cells look like and how they respond – we have a sort of identikit for Wally. I hope that our work will allow us to give people at risk of type 1 diabetes more certainty about whether they are likely to develop the disease and also give us a way to test the efficacy of new treatments as they come online.”
Medical orphans find a home
Clinician-researcher Ramin Shayan spends his research time trying to do himself out of a job. Ramin’s work in SVI’s O’Brien Institute Department is focused on understanding the molecular mechanisms of a condition known as lymphoedema – an increasingly common consequence of breast cancer treatment. He is also a highly sought-after plastic surgeon who has developed innovative surgical solutions for people with the condition.
“Happily, a growing number of cancer patients have had their life spared thanks to new therapies. But because of this there is also a growing cohort of people who suffer debilitating side-effects resulting from their treatment,” says Ramin.
Lymphoedema occurs when removal of lymph nodes or damage to the lymphatics system during treatment for cancer – mainly breast cancer or melanoma – causes lymph fluid to build up under the skin.
The condition can be debilitating, with an affected arm in a very bad case weighing up to 6 kilos more than an unaffected arm.
“Our approach to treating the cancer is so sophisticated, it is hard to imagine that these people often felt that they couldn’t get anyone to acknowledge the consequences of that treatment as a serious problem. These people were ‘medical orphans’ – there was no-one who was dedicated to understanding what caused lymphoedema, much less finding a way to treat it,” says Ramin.
Ramin’s list of patients has grown steadily since 2013 when he started performing complex surgery on these patients – painstakingly repairing damaged vessels in surgical sessions that can take up to 6 hours.
“Surgery allows me to see the problem at a microscopic level, but it is limited by the size and type of surgical instruments available, by my manual dexterity and also by the resolution of our imaging.
Molecular biology allows us to understand at a deeper level – at a cellular level – what is going wrong and will hopefully allow us to develop new ways to stop the problem from occurring in the first place.”
He says that he would happily forego his surgical work on these patients if he could develop a therapy to solve the problem before it became so serious that surgery was required.
Di shares her story
“In 1994, I had a routine mammogram that showed up a lump. Following the diagnosis of breast cancer, I had a lumpectomy, chemotherapy, radiotherapy and hormone therapy.
My family have always been very supportive. My mother’s mother and her sister had breast cancer many years ago, but I was the first in my immediate family to be affected.
One by one, however, the rest of the women in my family have been also been diagnosed with breast cancer. My mother was diagnosed in 1996, and received a second diagnosis in 2001. My twin sister’s turn came in 2003.
In that same year, I was diagnosed again and had a bilateral mastectomy, chemotherapy and hormone therapy.
In 2005 my twin sister received another diagnosis and in 2006 my older sister was told she had the disease. Genetic testing showed no sign of the BRCA1 or 2 genetic mutations – it is a real puzzle as to why we have all been affected.
I feel I cope well with the disease. I have a wonderfully supportive group of family and friends who try to keep me on an even keel!
In 1995 a support group was formed by friends who wanted to help me with my chemo and radiotherapy treatments. This group is called “Bosom Buddies”, and 23 years later, is still going strong! (bosombuddies.org.au) I have maintained an involvement with Bosom Buddies over the years, having served in different committee positions. I now belong to our Support Group, giving phone and personal support to women with breast cancer, and their families.
Like many people who have had a cancer diagnosis – and particularly with my family history – there is always a concern about future recurrences. But it is important to keep it in perspective: I have a wonderful oncologist and GP and I have regular check-ups.
I think it would be great if we understood more about the genetic component of breast cancer so we could understand why families like mine are affected. It would also be wonderful if the high success rate of breast cancer treatment – due to the successes of medical research – could be translated into treatments for other cancers which have very low survival rates, like pancreatic cancer.”
Image: Di, top left, with her mother and siblilngs
Passion for a healthier future drives bequestor
Bernadette Dennis, a long-term SVI supporter and member of the Jack Holt Society, shares her reasons for leaving a Bequest to SVI in her Will:
“My association with the St Vincent’s campus started when I was born at St Vincent’s Maternity Hospital, then located on Victoria Parade. Since I was one of eight children, our family became very familiar with the hospital! Many of my father’s friends worked at the hospital and it was where my sister started her nursing career in 1962.
I have only a very vague memory of hearing about a research institute. This changed, however, when the brother-in-law of one of my closest school friends became the director. SVI then became more familiar and although I lived and worked overseas for many years, I was able to follow its successes.
On one of my return visits to Melbourne, I attended a fundraising dinner at the Park Hyatt. From then on, through family and friends, I felt myself connected - as an advocate for SVI - and I continue to be in awe of the work of the researchers.
Over the past 14 years, I have had a sister and a brother die of cancer, and I have a sister with MS. Like us all, I have friends with Alzheimer’s disease, with cardiac challenges and with various disgusting cancers. We need to find cures and we need to see medical research become a community focus. This is why I have left a small Bequest to SVI in my Will.
A Bequest can advance the cutting-edge work of a scientist, provide a scholarship for a PhD student, purchase vital equipment to speed up a discovery or help develop a drug to treat Alzheimer’s disease, heart disease, cancer or diabetes. Bequests can be directed to a specific area of medical research, and can be named in honour of a loved one.
This wonderful medical discovery institute was a direct result of the Bequest left by Jack Holt. Just leaving a percentage of your estate is not about decreasing your family’s inheritance, but about providing them, and the community, with a healthier future.
For more information, or a confidential discussion about a gift to SVI in your Will, contact Kate Barnett, Chief Executive of the SVI Foundation, at [email protected] or (03) 9231 3265
Image: Bernadette Dennis, far right, with SVI Foundation Board Chair Karen Inge and husband George
2018 Women in Research Award
Dr Michaela Waibel, a type 1 diabetes medical researcher, is the recipient of the 2018 Susan Alberti Medical Research Foundation (SAMRF) Women in Research Award.
Proceeds from the SAMRF Annual Mother’s Day Luncheon held each year in May help fund the Award, which supports the work of an outstanding female scientist by covering the cost of a research assistant while she is on maternity leave.
“We have so many talented female scientists in medical research” says Susan Alberti AC. “It’s important that we put supports in place which can allow their work to continue while they’re on maternity leave.”
“I have worked so hard to get to this point in my research career,” says Michaela, “I’m very grateful to Susan Alberti and her supporters for acknowledging my work and providing this opportunity to ensure it continues. It is a relief to know that my research will carry on while I get used to my new role as a mother.”
Associate Professor Louise Purton was the keynote speaker at the sold out 2018 event.
A personal crusade
Christine Tarascio’s motivation is simple. She wants the SVI Discovery Fund she established a little more than a decade ago to help scientists continue their research into the most common and crippling of diseases.
But, like all great causes, there is a personal impetus to her ambition.
“One of my sons, Sam, has psoriatic arthritis, and I have seen the way he has had to manage that condition,” Christine says.
“My father also died of lung cancer. There is a large personal motivation for wanting to ensure scientists have enough money to tackle common diseases.”
It’s a personal motivation that isn’t confined to Christine, either, with many of the 100 or so members and donors to the Discovery Fund motivated by a close brush with disease.
“It’s a theme I have noticed with a lot of the supporters of the Fund,” says Christine, who is Chair of the Discovery Fund and an SVI Foundation Board member.
“They have all been touched in some way by illness or disease, whether it’s a close friend or family member who is sick. Sometimes they have had therapies or treatments themselves that would not have been possible without medical research. It becomes a big motivator in their commitment to the Fund.”
It partly helps explain, too, the exponential growth of the Fund since its inception. Earlier this year, the endowment fund exceeded its milestone of $5 million, helping to ensure researchers can be supported in perpetuity.
“We started off by inviting people to give $10,000 for 5 years, with each donating $50,000 all up,” Christine notes. “We now have 45 members of the Fund and many are on to their third term of donations.”
During the early years of the popular annual Discovery Fund lunch, Christine would host the donors and scientists at her home.
“I would push the furniture out of the living room and into one of the bedrooms,” she says.
“Then the gathering got too big, so now we go to a restaurant and then back home, which is where the real party starts. The donors love hearing from the scientists, who are unbelievably humble and thankful for the money we’re raising, but, really, we’re the ones thanking them for the important work they’re doing.”
The endowment fund model will ensure a steady income stream for SVI researchers by enabling a reliable cash injection through income generated from the Fund.
“In a way, it’s filling the gaps in traditional grant funding,” Christine says. “You need to have a grander vision and look for ways to guarantee income further down the track.”
Christine is not about to rest on her laurels either, and can’t see why the Fund cannot reach a $100 million milestone one day.
“The greater the endowment fund, the greater the income for the scientists,” she says.
“I can feel that it’s going to be a phenomenal success. I really do believe that the sky is the limit.”
A year in pictures