Meet some of the researchers funded by the Trish Foundation
Meet some of the researchers funded by the Trish Foundation
Searching for a cause…and a cure
By Lisa Burling and Paige Pollard, LBPR
As the influential former US First Lady Eleanor Roosevelt once said, “We do not have to become heroes overnight. Just a step at a time, meeting each thing that comes up, seeing it not as dreadful as it appears, discovering that we have the strength to stare it down.” And that is certainly true when it comes to the steps and challenges of understanding and researching Multiple Sclerosis (MS).
One scientist taking a step at a time to understand the exact cause of MS is Dr Jessica Fletcher. With a PhD and a Bachelor of Animal & Veterinary Bioscience (Honours I), both from the University of Sydney, she admits it is these exact challenges that keep her so passionate and driven in her research.“MS is a complex disease that involves an interaction between the immune system and the nervous system, which are two entirely separate systems of the body. This makes MS a challenge to both understand and to treat, however this also makes it immensely rewarding to do.”
Dr Fletcher’s passion in this area came to light when she first started her career in animal genetics. This was during her PhD at the University of Sydney when the diseases she was studying had changes in genes that controlled the myelinating cells (oligodendrocytes). She wanted to know more about how myelin is made, and more importantly what happens when it becomes damaged and isn’t there anymore.
“I found this super fascinating and was surprised by how much we did not – and still do not – know. This is why I work in this area and I am focused on understanding what happens when the myelinating cells are damaged and trying to find ways to use what we know about oligodendrocyte myelination to promote repair,” she says.
The next big step in Dr Fletcher’s career was the sponsorship of her postdoctoral fellowship by the Trish Foundation, during which she found that using a peptide called TDP6, designed to mimic the growth factor brain-derived neurotrophic factor, could stimulate and enhance myelin repair in a mouse model of MS.
Fast forward to today, Dr Fletcher is part of the team at the Melbourne Brain Centre at the University of Melbourne and works alongside the best myelin biologists and MS researchers in Australia. “I am still early in my career, but a key highlight in my career journey so far has been joining the team at the University of Melbourne in the Melbourne Brain Centre,”, she says. “This is where the best myelin biologists and MS researchers in Australia are from and I have learned and grown so much as a scientist in this environment.”
Currently working on a project that aims to develop a new animal model which can test remyelinating therapies, Dr Fletcher and her two fellow researchers are aiming to better understand what happens to myelin repair in people with MS.
Dr Fletcher explains: “We are currently performing studies to see whether our new model of failed myelin repair responds to our candidate remyelinating therapy, TDP6. Overall, what we are doing is establishing a new tool which can be used to test the potency of remyelinating drug candidates in an animal model that more closely replicates what happens to myelin repair in people with MS.”
Like most scientists, there isn’t a “typical” day of research in the lab for Dr Fletcher, but she says that’s exactly what brings her so much joy in that every day is different. When she isn’t looking after the animals, attending team meetings, carrying out microscopy and image capture or preparing samples, you will find her at the computer doing what she loves – data analysis and evaluating whether their hypothesis was correct! The rest of her time is filled in by engaging with what other groups are doing.
“Engaging with others helps us stay at the forefront of research and adapt to new findings which can change our perspective on how MS or myelin repair occurs. It’s also fulfilling to share our work with other researchers and the public through talks and presentations.”
For someone who is an incredibly busy person, she doesn’t stop there. Truly making best use of the 24-hours we have a day, Dr Fletcher finds time to disconnect so she can move her body, whether it be on a reformer or whipping up a delicious healthy meal.
“Staying active is important to me, so you would probably find me doing a Pilates class or going to the gym. I’m also into cooking, so I’m often found in the kitchen or specialty supermarkets.”
As we take one research step at a time in the journey towards a world in which no person should suffer or lose their life to this insidious disease, Dr Fletcher says she believes it is critical to understand what causes MS.
“There are a whole bunch of very smart, passionate scientists and researchers out there who are investigating ALL aspects of MS, but despite the diversity of research we pursue, as MS researchers we are all very focused on our goal to improve outcomes for MS patients and to stop this disease in its tracks. For almost all diseases that have treatments that stop them in their tracks we understand the primary cause or trigger. This is something that is still missing for MS research.”
By Lisa Burling, LBPR
If you ever have the privilege of asking a researcher about their work into multiple sclerosis (MS), more often than not they will start at the beginning and draw you into a conversation that has the potential to for last hours before the conclusion is reached.
Ask A/Prof Kaylene Young – Senior Research Fellow, Menzies Institute for Medical Research at the University of Tasmania – about her research into MS, and she immediately takes you to the end.
“A cure. While I think interventions that improve MS management are important interim measures, I don’t think we should aim for anything short of a cure – and I truly believe that we need to understand what causes MS before we can cure it.”
Like many scientists, A/Prof Young says her interest in science as a profession initially came from something very personal.
“When I was in high school in Tasmania, I really enjoyed maths and science subjects, but it wasn’t until my grandmother lost her battle with cancer, two weeks before my 16th birthday, that I really started to think about pursuing a career in the biological sciences and medical research. Brains are amazing things.”
Fast forward to her years as an undergraduate student at Monash University, and A/Prof Young admits to finding neuroscience lectures fascinating. “At the time, I read a report from the Walter and Eliza Hall Institute, that had been published a few years earlier, saying that stem cells exist in the adult brain. The senior author of that paper, Professor Perry Bartlett, agreed to take me on as his PhD student.”
“Like many researchers, I came into my field because it interested me, and I have stayed because I could see the potential benefit of the work I was doing.”
From starting in neural stem cell biology, A/Prof Young says it was a short jump to see the potential application of new knowledge about oligodendrocyte progenitor cells for the treatment of MS. The Trish Foundation, through its relationship with MS Research Australia, supports A/Prof Young’s current project grant (2017-2019) aimed at “Enhancing brain activity to re-wrap nerve fibres”.
A/Prof Young explains: “As part of this research project, we have shown that a non-invasive technology, called transcranial magnetic brain stimulation (TMS), can increase the survival of new oligodendrocytes added to the nervous system, and we published these research findings in early 2019. This project also includes a preclinical trial, in which we have been investigating the ability of TMS to increase the number of new oligodendrocytes to repair brain lesions, and the outcome of this work is still pending.”
A/Prof Young is refreshingly honest about the challenges associated with conducting studies; she quickly debunks the oft-held view of the lay person that researchers get excited every day by a new discovery.
“Each day doesn’t have a “eureka” moment; it is often a long process to get to that point. A lot of science involves overcoming technical challenges to be able to perform a study, or being very precise as you perform an experiment today, in exactly the same way you that performed it yesterday, to collect the data that you need. It also involves a lot of reading, to stay on top of the discoveries of other scientists and apply that knowledge to your own research.”
However, it’s clear that being surrounded by equally dedicated and passionate researchers contributes enormously to A/Prof Young’s passion for her work. Her team is based at the Menzies Institute for Medical Research at the University of Tasmania and consists of three postdoctoral researchers, one research assistant, seven PhD students, and two honours students. MS research is a priority research area within the Institute, and her team of laboratory researchers works closely with other MS research teams that look at the genetic, public health, health economic and clinical aspects of MS research.
“I get to go to work every day and interact with enthusiastic and talented researchers in an environment that values innovation and discovery.”
“I really enjoy working as part of an MS research team, in a Research Institute with a strong MS focus, discussing new ideas about MS with my students and staff, and planning the new research studies. I also like that once the experiment is completed and the data is decoded, you are the first people in the world to know the answer to your question.”
Unsurprisingly for someone who’s profession is also her passion, A/Prof Young spends a lot of time at work. However, when she does take time out, she gravitates towards the outdoors – away from labs, laptops and mobile reception. She loves hiking, but that doesn’t always mean that she is away from science.
“I recently hiked in the Swiss alps, along the side of a very large glacier, accompanied by a Swiss research collaborator, so we spent a lot of the day talking science and discussing our latest research findings, but we did it surrounded by beautiful scenery.”
American composer Duke Ellington famously said “A problem is a chance for you to do your best”, a sentiment certainly shared by Associate Professor Peter Crouch in the Department of Pharmacology & Therapeutics at Faculty of Medicine, Dentistry & Health Sciences at The University of Melbourne.
“I think every scientist is naturally drawn to problem solving and that’s definitely true of me. I love the opportunity to get my teeth stuck into problems to solve and really enjoy the scientific process of coming up with ideas then testing their veracity with the right experiments. I’d be happy trying to solve relatively esoteric problems, but when there’s a real need out there for the answers that we’re trying to generate, that really gives me the extra drive.”
A/Prof Crouch’s research into Multiple Sclerosis (MS) focuses on the progression of the disease, so his ambition and that of his team is to develop the drug that stops the progression.
“Obviously, the ultimate goal for progressive MS would be to find the treatment that is completely restorative, but I think finding the drug that can stop worsening of symptoms would be a pretty good start,” he says.
Currently working on a three-year project, supported by the Trish MS Research Foundation and MS Research Australia, that aims to better understand the role of the micronutrient copper in progressive MS, A/Prof Crouch and his fellow researchers are aiming to better understand the extent of copper-related changes in human, progressive MS tissue and to explore the full potential of their therapeutic strategy.
“Copper is essential for all forms of life; in people it is needed in every cell throughout the body. Prior to starting this project we had identified that the natural requirement for copper is shifted in progressive forms of MS and that a copper-containing compound provides positive therapeutic outcomes in animal models of MS,” he explains.
It’s often said that whatever you liked doing as a child is a nudge from your soul as to what you should pursue as a career – do what you love and you’ll never work a day in your life! Wisely, A/Prof Crouch took this approach when considering going to university and choosing his degree.
“I thought about the subjects at high school that I enjoyed the most and I always enjoyed biology, so when I started looking into courses available at different universities I was immediately keen on the course offered at La Trobe University where I could do pure biology for the whole three-year degree. I loved every minute of it, and when I found out that you could become a professional scientist via Honours then a PhD, I knew I’d found the career for me. I’ve been working in labs full-time since 1997, and I still love every minute of it.”
Although no day is “typical”, A/Prof Crouch feels comfortable wearing a lab coat and loves being in the lab. His ideal day involves getting to work super early in the morning, going straight into the lab, then spend the entire day in the lab doing experiments. A common theme is doing what needs to be done so that his team can keep doing the lab work as there’s a lot that needs to be done just to keep the lab operational and to maintain the work flow: “If I can do as much as possible to ensure that the people in my team keep generating data, that’s a good thing.”
That said, career highlights for A/Prof Crouch go well beyond the lab and across borders. “I have had the opportunity to meet people across the globe; a few jars of beer and a bit of science talk is pretty nice, and being able to do it in amazing places like Tokyo, Padova, Taipei or Glasgow is definitely enjoyable.”
He adds that highlights are always those moments when his work and that of his team is validated: “Making a new discovery is great, but having an independent group validate your findings is very rewarding.”
A/Prof Crouch also highlights the role of collaboration in achieving success in his research projects, including those centred on MS: “We’re very fortunate to have direct access to some pretty amazing technical resources, as well as some very talented scientists and clinicians, not just in neuroscience and neurology, but across many different disciplines. The work we do extends well beyond my immediate team, so if we’re successful in our endeavours, our success will come from the collaborative partnerships that we’ve formed, not just the experiments that are done within my lab.”
With a family made up of his beautiful wife and two kids, and an old cat who’s now blind, outside of work A/Prof Crouch is a self-confessed home-body.
“I really enjoy rainy days at home when we all get cosy inside and spend some quality time together. But if we were to venture out and about, camping trips are always a favourite, especially in amongst tall trees. In summer, my favourite, self-indulgent, spare time activity is listening to test match cricket on the radio.”
When you ask Dr Natalie Payne – Research Fellow in the Nagy Laboratory at the Australian Regenerative Medicine Institute (ARMI) – about her motivation for focusing on Multiple Sclerosis (MS) research, her answer immediately reveals a passion for her work that extends well beyond the petri dish.
“Like many scientists, I have a pure love of trying to understand complex biological processes. But ultimately I hope that the work I do will contribute towards improving the life of people with MS and more broadly to individuals suffering from other health conditions. It’s an exciting and transformative time to be in biomedical research due to the rapid pace in technological advancements.”
Dr Payne has always had an interest in biology and understanding human disease. However, it wasn’t until she began her PhD in Professor Claude’s Bernard research group at the Monash Immunology and Stem Cell Laboratories just over a decade ago that she found MS was an area of research she was really passionate about pursuing as a career.
“MS is a complex disease and it is clear that we cannot treat it by simply suppressing the immune system. Being able to manipulate the immune response to be reparative rather than destructive is a concept I find fascinating. It’s extremely relevant to understanding and successfully preventing progression of MS.”
Dr Payne has undoubtedly chosen a career path that suits her talents, skills and expertise – she was awarded the Bruce Stone third year Biochemistry prize for the top mark in third year biochemistry during her undergraduate degree at La Trobe University, and a Trish Foundation PhD scholarship in 2007. Dr Payne has gone on to be recognised with a number of other accolades for her outstanding contribution to MS research including the Monash University postgraduate publication award in 2011 and the MS Research Australia Ian Ballard Travel Fellowship in 2013.
“Being able to manipulate the immune response to be reparative rather than destructive is a concept I find fascinating. It’s extremely relevant to understanding and successfully preventing progression of MS.”
Dr Payne has also been successful in securing a number of incubator grants – one in 2015 to characterise iPSC cells from MS patients, which is currently being prepared for publication; and two incubator grants in 2017, both funded by the Trish Foundation.
One of these incubator grant funds a collaborative project led by Dr Claire McCoy, which aims to investigate a molecule involved in switching a specific immune cell type from an inflammatory tissue-destructive phenotype to a regenerative phenotype associated with remyelination. Dr Payne is the lead investigator on the second incubator grant project, which is focused on using gene-edited stem cells to deliver therapeutic proteins.
Dr Payne explains further: “We have modified cells at the DNA level so they can be used as mini-factories that pump out therapeutic proteins after receiving an “on” signal. Our approach is possible because the cells have also been modified with a safety switch that controls their proliferation and therefore alleviates the safety concerns surrounding the use of cell therapies in patients.
“Our current research aims to apply this approach to MS, by creating cellular mini-factories to deliver a naturally occurring protein (interleukin-1 receptor 2, IL-1R2) that can “mop up” IL-1β, an inflammatory molecule that promotes neuroinflammation and neurodegeneration in MS. We have successfully engineered cells to produce IL-1R2 in an inducible manner and are now using different experimental models to determine how this approach to blocking IL-1β impacts the immune response and tissue damage within the central nervous system.”
Dr Payne and her team have applied for additional funding to the National Health and Medical Research Council (NHMRC) and the CASS Foundation in Australia, and the National MS Society in the US.
“This additional funding will allow us to develop cellular mini-factories that can be transplanted into patients of diverse genetic backgrounds without being rejected by the immune system, as is observed when organs are transplanted between individuals.”
A typical day for Dr Payne and her team in the lab is largely focused on cell-based therapies, so it always includes looking after the cells they have in culture – checking them under the microscope, feeding them, and replating them into new tissue culture dishes so they have room to grow.
“We have engineered our cells to perform novel functions and so they must be tested and validated using different laboratory models”, she explains. “These experiment can take anywhere from a day to several months if the gene modified cells are being tested in animal models of MS.”
Aside from laboratory based work, much of Dr Payne’s time is spent at the desk analysing data, writing grants, reading papers as well as meeting with students and collaborators to plan experiments, as well as attending seminars.
When not undertaking her incredibly important MS research work, Dr Payne can be found with her husband Cameron and their 4-year-old daughter Alana on their 5.7 acre property outside of Melbourne. She relishes spending time outdoors when so much of her work is spent inside.
“We moved here from a two bedroom flat in the inner city three years ago; it’s a completely different lifestyle but I love being able to enjoy time outdoors and the native wildlife, especially since there are many working days when I don’t get a chance to go outside.”
“I think being able to reverse the damage and neurological disability in MS patients is the holy grail of MS research.”
Dr Payne believes being able to reverse the damage and neurological disability in MS patients is the holy grail of MS research.
“For this to be successful we need a multifaceted approach that includes understanding how we can influence the immune response in MS to promote repair. This is an area that is of great interest to me.”
For Dr David Gonsalvez National Health and Medical Research Council / MS Research Australia Betty Cuthbert Fellow at the Department of Anatomy and Neuroscience, University of Melbourne – the holy grail of Multiple Sclerosis (MS) research is two-fold. “For me, it’s understanding exactly by what mechanism MS occurs and finding a way to prevent the disease altogether – or a suite of treatment options to halt the progressive component of MS.”
Dr Gonsalvez is driving an exciting and important research project entitled “Promoting myelin repair by targeting Wnt signalling” which the Trish MS Research Foundation is honoured to be co-funding with the National Health and Medical Research Council.
Working with Co-Investigator, Dr Junhua Xiao in the neurotrophin and myelin laboratory, Dr Gonsalvez will identify the way that Wnt signalling affects the cells which produce myelin and determine whether blocking the Wnt pathway and its inhibitory affects might then promote myelin repair.
“Myelin is the conductive layer present around nerve fibres in the brain and spinal cord, and damage is caused by inflammation brought about by the immune system mistakenly attacking myelin. This important research project will determine the molecular characteristics of this pathway within the chronic lesions to isolate targets that might have therapeutic potential in future to slow the progression of MS,” he explains.
Dr Gonsalvez admits he’s always had a curious mind and been intrigued by science: “I can still remember the first time I looked down the old zeiss microscope at a slide I had stained; I was totally captivated by the colours and how beautiful this piece of neural tissue looked. This simple technique could be used to answer so many questions and I thought it was totally amazing. I still do.”
However, it was an experience via a family member that really catalysed and fuelled Dr Gonsalvez’s passion to pursue a career in science. His uncle, Dr Mario D’Cruz, was in the Fellowship year of his general surgical training when he had a car accident which left him quadriplegic.
“I moved in with my Uncle Mario after he returned home from rehabilitation. I happened to be completing my undergraduate studies and was one of his carers. His medical background and my study in neuroscience lead to fantastic discussions about the nervous system, it became pretty clear to us both how little we humans actually know about the brain. In addition, witnessing how he could just get on with life and continue to enrich his friends, family and the experience of other people with similar injuries was totally inspiring.”
Dr Gonsalvez continues: “I wondered how some brains, like Mario’s, have the capacity to respond in this way to circumstances that others can’t move past. Not only did this make me even keener to learn as much as I could about the brain and human body, it also instilled a resilience you need if you want to be a scientist today.”
Whether creating knowledge resulting in the better understanding of biological processes of disease, identifying novel therapeutic targets, or developing practical applications, Dr Gonsalvez admits he finds it easy to be motivated and passionate about what he does.
“When you know your efforts are directed toward contributing in some way to ultimately improving the outcomes for people with MS, passion and drive are not hard to muster. In addition, motivation and passion can be contagious; it’s easy to catch when you are around engaged people working at a common goal.”
Outside of the laboratory, Dr Gonsalvez is equally passionate about his family, as a proud husband to Raylyn and doting Dad to two small children – Harper, 2 and Otis, 3 months. He’s also a keen guitarist and loves busting out the old blues tunes, when The Wiggles get a break from being top of the set list!
Dr Steven Petratos is very clear with his response when asked why he is so passionate about Multiple Sclerosis (MS) research and his part in the quest of the global scientific community to find a cure.
“I have always promised myself that I will never give up investigating the devastating disease that my grandfather suffered from.”
That sentence links Dr Petratos even more closely with the work of Trish MS Research Foundation, set up by Trish’s parents Carol and Roy Langsford after they made the same promise to their daughter – they wouldn’t give up until a cure was found.
“MS is an insidious neurological disease commonly induced by the specific destruction of the protective sheath of nerve fibres, known as myelin. MS affects approximately 2.5 million people worldwide, with debilitating consequences; currently, the best therapies can only limit relapses in patients, but as these individuals age with the disease, they become vulnerable to progression. I am driven by a desire to provide a better quality of life for people living with MS,” comments Dr Petratos.
The Trish MS Research Foundation is pivotal to Dr Petratos’ latest research project, providing funding at the most critical stage. Supported by the Trish MS Research Foundation in affiliation with MS Research Australia, he is investigating the therapeutic blockade of the neurodegenerative mechanisms that govern progressive MS. In this funded project, Dr Petratos’ team has designed a new stem-cell based therapeutic strategy in an attempt to limit
the progression of MS and enhance repair of the central nervous system.
“With the support of previous MS research funding, we have made great advances in the understanding of why MS can progress to permanent disability. We have since designed specific ways to directly target the disease epicentres where damage occurs to the brain and spinal cord, thereby protecting these areas from further damage and enhancing repair. The Trish MS Research Foundation is now helping my team achieve the proof that this stem-cell based therapeutic approach will indeed limit the progression of MS.”
Dr Petratos’ career in MS research started as an undergraduate at the University of Melbourne, where he embarked on an Honours degree and then subsequently a PhD in antibody-mediated demyelination. This then lead into post-doctoral research projects in demyelination and repair of the peripheral and central nervous systems, which has now culminated in his current research interests of regenerative medicine specifically in MS.
“During my early undergraduate University candidature, I was always fascinated in how the immune system interacted with the central nervous system,” he says.
Dr Petratos’ research projects have been supported by a range of credible organisations, including MS Research Australia, the National Health and Medical Research Council (NHMRC), the National Multiple Sclerosis Society in the US, and the Trish MS Research Foundation.
His PhD work on myelin damage in HIV-infected patients was supported by receiving one of only 13 Commonwealth AIDS Research Grants (CARG) from the National Health and Medical Research Council.
His Postdoctoral work in nerve fibre and myelin damage was first supported by a MS Research Australia project grant then followed by an inaugural Trish MS Research Foundation project grant in 2002.
Dr Petratos has since gone on to receive two post-doctoral fellowships from the Faculty of Medicine, Nursing and Health Science at Monash University, followed by an NHMRC Project grant to investigate neuron damage in brain diseases. These investigations lead him to identify the abnormal modifications of an important neuronal protein called CRMP2 that only occurs during brain disease and is fundamental for the normal function of neurons when unmodified.
Dr Petratos is also a proud member of The International Progressive MS Alliance – an unprecedented international initiative that is connecting resources and experts around the world to find answers and develop solutions to end progressive MS. In fact, Dr Petratos is the sole Australian recipient of funding from The International Progressive MS Alliance, supporting his current project with the Trish MS Research Foundation and MS Research Australia.
“The goal of the Alliance is to speed the development of new treatments for progressive MS by funding the best research, wherever it exists. By establishing global research priorities, the Alliance is poised to speed progress to identify solutions to address this urgent need. Collaboration among all stakeholders in the MS community is a critical element required for our success. Partnership between academia and the pharmaceutical and bio technology industries is essential to meeting the goal of the Alliance as academia provides knowledge generation and industry has the extensive resources and research talent needed to drive large-scale advancements in progressive MS,” Dr Petratos explains.
Unsurprisingly, Dr Petratos has a heavy schedule as Head of the Regenerative Neuroscience & Development Group at Monash University. Although a typical day doesn’t exist, he can often be found discussing findings of recent experiments his PhD students performed, interpreting data, designing future experiments, preparing data for presentation and publication, and discussing collaborative projects with scientists and clinicians in Australia and overseas.
Outside of the laboratory, Dr Petratos likes to spend his spare time with family – wife Andrea and children Elizabeth and Anthony – and friends, enjoying their company and validating how special they are to him.
When you ask a dedicated and hard-working scientific researcher what three things he’d take to a deserted island, it’s no surprise to discover two items are the ultimate in relaxation, but one is completely focused on getting back to his life and his work.
“What would I take with me? Sunglasses, a hammock, and a kayak – to enjoy the waves and then to escape when the time is right,” confesses Dr Lawrence Ong, who is undertaking his first research project funded by the Trish MS Research Foundation. He has been awarded the Betty Cuthbert Postgraduate Scholarship co-funded by National Health and Medical Research Council (NHMRC), and MS Research Australia. This prestigious Scholarship is 50 per cent funded by the NHMRC, with the Trish MS Research Foundation fully funding the MS Research Australia component.
In simple terms, Dr Ong is focused on trying to understand why individuals develop MS and his scholarship, funded by the Trish Foundation, will allow him to pursue research, without the distraction of full time clinical work.
“We know that there are both genetic and environmental risk factors that appear to play a part, but we don’t understand all of the specific mechanisms which ultimately result in disease”, expands Dr Ong. “My project is trying to understand why MS risk seems to be set in childhood and adolescence. Current research suggests that this is related to latitude and Vitamin D, but why this is, is unclear. I will be using gene sequencing technology to try and help answer this question.”
Dr Ong’s laboratory is based at the Westmead Institute for Medical Research on the Westmead Hospital Campus in Sydney. It’s been an ideal start as he also trained at Westmead Hospital as a medical student, plus completed most of his Immunology training there.
“Our group’s specialty is immunogenetics, so we incorporate both immunological and gene sequencing techniques in our work. It is an exciting field to be in, because the technology is developing so rapidly and being applied to questions that could not previously be addressed with the tools available. This has led to new discoveries which are being made at a very rapid rate,” Dr Ong says.
“The breakthroughs that have been made in understanding MS have been inspirational, and our laboratory has been involved in some of the major ones, pinpointing specific risk genes in MS. There are still so many questions to be answered, but there is an expectation that the rate of discovery will only keep gaining pace.”
Like many people who excel in their chosen field, Dr Ong’s passion for science and discovery was with him from a very young age. “I always imagined myself as a scientist; I studied maths, physics and chemistry at high school and then psychology at University. During my medical degree, I was fortunate enough to receive scholarships which allowed me to pursue placements in rural and regional Australia as well as in Vietnam. This allowed me to see the diversity of medical practice and medical systems that exist. It also reminded me of how lucky we are to have access to such good medical care here in Australia.”
Having recently celebrated his first wedding anniversary, Dr Ong has very little spare time for activities outside of his research, but recognises the importance of striking a balance, as external influences foster fresh ideas and motivation.
“I love spending time outdoors which usually happens on my bike or in a kayak. I’m currently training for a three day bicycle ride from London to Paris in July. At home, I like to think I’m somewhat handy in the garden, having cultivated some ultra-spicy habanero chillies and glossy eggplants this year!”
Dr Ong joins his fellow scientific researchers in believing a cure for MS is not far away: “If we can work out the mechanisms which lead to people developing MS, a cure will be that much closer.”
Growing up, Dr Fiona McKay was fascinated by the human body and watched a lot of surgery documentaries. Now the mother of two is working to find a cure for MS.
Photo courtesy Benjamin Lee Photography
Dr McKay, a Research Officer at the Centre for Immunology, Westmead Millennium Institute at the University of Sydney, was awarded an Incubator Grant by the Trish MS Research Foundation earlier this year to explore how genes predispose a person to MS – something she has been working on for the past decade. She joins an impressive line-up of researchers who are working to piece together the puzzle of what causes MS in the hope of finding a cure.
The Incubator Grant is designed as start-up funding to help nurture and explore new ideas in the world of MS research. Dr Fiona McKay’s work is exploring the idea that the genes that predispose someone to MS might do this by making them more susceptible to the Epstein Barr Virus (EBV).
Dr McKay comments: “EBV is the virus that causes glandular fever, but it has also been associated with MS and we don’t really know why. The jury is still out on whether EBV is really involved in causing MS, or whether it is more active in MS purely as a side-effect of having a chronic inflammatory disease.”
Dr McKay’s current work is inspired by the work of leaders of the Westmead Millenium Institute at the University of Sydney where she works. Professor Graeme Stewart and Associate Professor David Booth were heavily involved in a huge International MS genetics study, comparing over 10,000 people with MS with 20,000 healthy people. The Trish Foundation made a contribution to the study’s remarkable findings.
She comments: “I work with a bunch of really talented and committed people at the Westmead Millennium Institute and Westmead Hospital. The leaders of the Westmead team were key players in an international MS genetics study.”
“As a result of this massive effort, we now know over 110 genes that predispose people to MS. It’s such a rich source of information, and we’ve only just touched the surface exploring what it can tell us about MS. The next step is to find how these genes predispose to MS, and that’s where the project generously funded by the Trish Foundation comes in.”
The opportunity to work in MS research started for Dr. Fiona McKay with a post-doctoral position 10 years ago working on how genes predispose a person to MS – and she’s been exploring this idea ever since.
“I’m passionate about MS research because it changes lives. In the last 10 years, the treatment options have trebled in Australia as a direct result of medical research. The speed of progress gives me hope that we’re getting closer to a cure.”
Her passion for MS research stems back to her university days studying a Bachelor of Science (biological sciences) and a then a PhD in microbiology at the University of Wollongong. She recalls “learning as an undergraduate at University how the immune system in multiple sclerosis (MS) attacks the conductive sheath surrounding the nerves of the brain and spinal cord, but no one really knew why. I thought it was a fascinating and much-needed research area”.
Life isn’t all lab coats and test tubes for this scientist at the forefront of MS research. These days Fiona works as a part-time scientist and is also mum of two little boys, aged 3 and 6, who although keep her world chaotic and sleep deprived, she believes her life is richer than she could have ever imagined.
Reflecting on her role as a mum, she says: “Perhaps the biggest surprise of parenting for me has been the way it leaves you so vulnerable. The love is so intense – you agonise over their everyday anxieties and your heart takes flight with every little screech of delight or ‘I love you’.”
She continues “I think all parents of small children giggle at the term “balance”; I think you ride the chaos and give thanks for the little wins… like when you arrive somewhere and Batman has not screamed the whole way or undressed himself in the car, or when you string together 6 hours of sleep.”
Fiona and her partner make a dynamic duo, both juggling successful and busy careers with parenthood. “I have a very good-humoured and patient partner who not only works full time but is also great in the kitchen and folds washing” says Fiona.
“I currently work part-time and am so grateful for a family-friendly and flexible workplace and for understanding mentors. Science is hard work but fascinating, fun and so worthwhile when you’re working on a disease like MS, so I consider myself very lucky to be able to continue while parenting littlies.”
A note from Dr Fiona McKay about the Trish MS Research Foundation:
The Trish Foundation that funds my research was established by Roy and Carol Langsford, who watched their daughter Trish struck down in the prime of her life, and ultimately lose her battle with MS in 2002 at the age of 30. I can’t quite imagine how one survives the loss of a child. Yet Roy and Carol have turned this horrible personal tragedy into hope for other people with MS. They and their team of volunteers formed the Trish Multiple Sclerosis Research Foundation with a simple and specific goal – to find a cure for MS.
“What do you want to be when you grow up?”
Most of us can remember being asked this question countless times by family, friends and acquaintances, as time catapulted us towards adulthood and the need to have a suitable response.
For some, it can be very hard to know the answer. But for Research Scholar and PhD student Jae Lee, his likely career path was clear from an early age, representing the perfect combination of his parents’ professional backgrounds.
“My mum is an amazing nurse and dad is a successful engineer. They heavily influenced me and I was into science and mathematics from a young age. When I was deciding on a career, I followed what I was good at to fulfil my ambition in scientific research.”
In 2010, Jae received a Bachelor of Biocellular Engineering With Honours from the University of Melbourne. After a short work experience internship at the Samsung Advanced Institute of Technology in South Korea, he started his doctoral studies at Monash University under the supervision of Dr. Steven Petratos (who was a recipient of funding from the Trish Foundation as part of the inaugural funding round in 2002). Jae currently works in a team with Dr. Petratos, two research assistants and two other PhD students.
Jae received funding from The Trish Foundation in 2013 for his Postgraduate Scholarship entitled Targeting the molecular mechanisms of axonal degeneration and de-remyelination in multiple sclerosis.
He explains more about the research project: “Our team have already shown that during MS and MS-like model, there is an alteration in protein called CRMP-2. By inhibiting this alteration of CRMP-2 during MS-like animal model, we showed that it is possible to halt nerve fibre being degenerate. We are going to extend our study to be translated into clinics by applying novel genetic technology and stem cells to effectively deliver this approach as a therapy during disease.”
Like many MS researchers, Jae’s interest in research projects in this area is driven by the search for a cure.
“During my bachelor degree, I was very interested in neurodegenerative diseases, particularly MS. I extended my studies by taking a project related to neurodegenerative disease during my honours. From then, I realised even though there are more people diagnosed with MS every day, there is no effective cure yet. This pushed me towards MS research and I was very lucky to meet my supervisor who is such a brilliant MS researcher, Dr. Petratos.”
Jae’s usual day at work is from 9am to 8pm in the lab and, after hours, he reads journal articles related to MS research to ensure he is updated on developments in the area. These long hours may explain why he confesses that we’d find him “enjoying drinking a nice cup of coffee” in his spare time! He also enjoys travelling around rural areas of Australia when his schedule permits a break.
His ultimate goal as an MS researcher is “to fully understand the mechanism behind nerve fibre damage during MS, by combining cutting-edge engineering technology and integral biology.”
We certainly have Mr and Mrs Lee to thank for Jae’s decision to focus his professional career on better understanding MS and, ultimately, joining fellow researchers who are dedicated to finding a cure.
The Power of Proteomics in MS Research
For many people, deciding which career path to embark upon once high school finishes can be confusing and daunting. But not so for Dr Linda Ly, a Postdoctoral Research Associate of Medicine, Central Clinical School at the University of Sydney. It was clear that science, specifically proteomics, was destined to be her professional passion when the final school bell rang.
“Finishing high school and choosing what courses to enrol in at university made me realise I wasn’t really interested in anything else except science. I undertook a Bachelor of Science degree in Biotechnology at the University of New South Wales and it was during my Honours year, the final year of my undergraduate degree that my interest grew in the budding field of proteomics; a discipline that involves the systematic study of all proteins within biological systems such as cells, tissues and fluids. Realising the potential of proteomic tools and techniques to answer biological questions, I then pursued a PhD following my undergraduate studies at the same university learning more about proteomics and how to identify and quantify the many hundreds of proteins present in biological samples.”
Dr Ly works with Dr Michael Barnett and Dr Ben Crossett at the University of Sydney, along with research assistant Ms Twishi Gulati. The Trish Foundation is proud to be funding Dr Ly’s Post Doctoral Fellowship which aims to better understand the repair mechanisms in multiple sclerosis (MS).
“In MS, symptoms correlate with focal areas of inflammation and demyelination – a process where myelin, the fatty tissue that normally wraps around the axons, is destroyed – in the brain and spinal cord. Remyelination is a process where the damaged fatty myelin sheaths surrounding the nerves are repaired, which plays a critical role in remission of the neurological symptoms that characterise MS. However, there is a progressive failure of this repair process as the length of time a person has had MS increases, which contributes to irreversible disability.
Dr Ly explains further: “This project aims to use proteomic techniques to discover and characterise the proteins that are important in the repair of the central nervous system and its failure. The identification of these proteins may lead to more effective treatments to promote the processes of repair in MS.”
As a post-doctoral researcher within the MS research team at the University of Sydney, Dr Ly has presented at MS conferences in Australia and internationally. She has also had post-doctoral work, detailing a comprehensive proteomic methodology in processing MS tissue, published in peer-reviewed publication, Journal of Proteome Research.
With a busy work schedule that includes planning and performing experiments including data analysis, drafting manuscripts for publications, reading journal articles to inform her work, and supervising students in their projects, it’s hard to imagine Dr Ly has any ‘spare time’ to enjoy her passions beyond science.
Amazingly, she manages to squeeze in French studies at TAFE (“definitely a challenge but enjoyable!”) and hopes to put her language skills to the test one day by travelling around France. She also enjoys shopping, going to the movies and spending time with her family which “usually involves a lot of eating!”.
Dr Ly believes the holy grail of MS research is to find what causes the disease and understand the entire disease process. She says it’s the challenge of such a complex disease, with many things not yet discovered about it that keeps her so passionate her work in MS.
“We are still searching to discover what causes MS and why some people are susceptible. It’s the drive to find the missing pieces of the puzzle, no matter how small, that could give us a better understanding of the biological or disease processes of MS. It’s this thirst for knowledge that could lead to better treatments, prevention and a cure.”
Professor Graeme Stewart AM, husband, father, grandfather, all round good guy and one of the world’s most eminent scientists.
When at University, Professor Stewart knew he wanted a career in Medicine that included a strong element of research. His PhD was on the genetic factors that predispose to MS.
“I was hooked on MS research at that early stage and have continued the search for the MS genes since,” says Professor Stewart.
On 11th August 2011 Professor Stewart’s 35 year quest from PhD student to grandpa became a memorable day in the history of MS research. Professor Stewart was one of five governance members of the International Multiple Sclerosis Genetics Consortium (IMSGC) and led the Australian and New Zealand contribution.
Professor Stewart says funding from the Trish Foundation has for many years been central to the efforts in uncovering the genetic factors that contribute to the cause of MS and to working out how they do it.
“In 2007, under the expert guidance of A/Prof David Booth in our group, we shared with colleagues in the USA and Sweden, the discovery of the second MS gene, IL7Rα,” Professor Stewart said. “In 2009, as part of the ANZGene Consortium we were pleased to be involved with the discovery of two more MS genes.”
“Now, in 2011 we have been part of the international consortium that published recently in the scientific journal Nature the discovery of 57 MS genes. Our challenge now is to uncover exactly how these genes are contributing to MS and design new and better treatments based on this,” Professor Stewart continues. “At each step, in our laboratories at Westmead, funds from the Trish Foundation have been essential.”
Professor Stewart’s life’s work of expertise, dedication, hard work and passion has reaped amazing rewards for Professor Stewart, his colleagues and for people living with MS. This modest man deserves all the kudos which comes his way.
Having spent the early years of his career in Sydney, Professor Stewart worked for two years at Stanford University in California.
“I returned from Stanford in 1980 to head up the Department of Clinical Immunology and Allergy at the then newly opened Westmead Hospital where I have remained since,” said Professor Stewart. “In the mid 1990’s my research efforts had grown to the stage that I formed the Institute for Immunology and Allergy Research (IIAR).”
In 1996, the IIAR became one of the four founding research groups of the Westmead Millennium Institute, now the second largest research institute in NSW and one of the six largest in Australia.
“Westmead Hospital has become the largest teaching hospital in NSW and, with addition of the Children’s Hospital at Westmead, I have seen the Westmead Campus become a major force in medicine and medical research in Australia and internationally,” Professor Stewart explains. “It has been a source of great satisfaction to contribute to the development of such an international resource in the western suburbs of Sydney where I grew up.”
Married to his soul mate and best friend Margaret, who is a Dermatologist, for more than 40 years, Professor Stewart is proud of his children Sam and Jessica, both Law graduates, who no doubt take after their Mum and Dad, being smart and hard working. Sam is a management consultant with BCG and Jessica works in Aboriginal Health in which she is completing a PhD. Sam and his wife Gillian presented Graeme and Margaret with a source of much joy, their first grandchild, Toby now aged 17 months.
When not spending time with his precious family or at work at Westmead, when looking for Professor Stewart, one would find him in the ocean, swimming for the sheer pleasure of catching waves or competing in ocean swimming races along the NSW coast and overseas.
A ‘typical working day’ does not exist for Professor Stewart, but he says almost every day involves some aspect of patient care and some time talking about research.
Professor Stewart says anyone who knows someone with MS knows where his passion and drive comes from. “I want to be there on the day when we go to our MS Clinic and announce that a cure has been found.”
One has the feeling this skilled, hard-working scientist who has given his working life to MS research, will greatly enjoy that day of celebration.
“The ‘holy grail’ of MS research? Finding the cause, of course.”
This simple statement underpins the work of Associate Professor Helmut Butzkueven, a long-term and much valued research partner of the Trish Foundation.
Originally from Germany, Associate Professor Butzkueven’s interest in neuroscience and immunology dates back to his school days. Yet it wasn’t until he moved to Australia in 1984 that the decision was taken to make it his career – studying Medicine at Melbourne University and qualifying as a neurologist in 1999.
Associate Professor Butzkueven then went on to do a PhD in animal models of MS at the Walter and Eliza Institute.
“We still need to translate animal work to human drugs, and to my mind this kind of research translation is one of the most important challenges for MS researchers in Australia,” he comments.
The Trish Foundation is extremely proud to have co-funded Associate Professor Butzkueven’s first Post-Doctoral Fellowship with the NHMRC from 2006-2009. As the recipient of the inaugural Betty Cuthbert Fellowship, he established and managed the rapid expansion of an international online MS outcomes registry run out of the Royal Melbourne Hospital. This registry follows more than 16,500 MS patients worldwide, including over 2,100 Australians.
“This registry is an invaluable resource as it is beginning to answer some very important questions regarding the long-term outcomes of MS now, as well as the usefulness of MS treatments”, Associate Professor Butzkueven explains.
During this time, Associate Professor Butzkueven also collaborated with a network of Australian and New Zealand scientists focusing solely on genetics and MS research. “I am very proud to have helped establish a large collaborative genetics study which discovered two new MS-related genes and continues to contribute a lot to our knowledge of the genetics of MS”, he says.
Currently, the Trish Foundation funds Associate Professor Butzkueven’s research focusing on the molecule Dab2, produced by an immune cell type called macrophages.
Associate Professor Butzkueven explains: “Macrophages are the immune cells that probably do most of the permanent damage in MS lesions. We are testing whether Dab2 is important in brain injury in MS, using animal models. This work is incredibly exciting because, if we can learn how to reduce or switch off Dab2 levels, we might be able to reduce this damage.”
Professor Bill Carroll, Chairman of the MS Research Australia’s Research Review Board and Research Management Council confirms Dr Butzkueven’s work is of the highest order. “He is one of the most outstanding clinician/scientists working in Australia. He has been able to span the wide range of research between the laboratory and the bedside”.
Although a ‘typical working day’ does not exist, Associate Professor Butzkueven spends a lot of his time project planning and managing a lab focusing solely on human MS genetics and immunology at the Department of Medicine, University of Melbourne. He also works at two MS Clinics at the Box Hill and Royal Melbourne Hospitals; commencing in 2002, these clinics now see approximately 1,500 people with MS.
Married with two daughters aged 13 and 10, and the proud owner of a female dog, Associate Professor Butzkueven freely admits he’s ‘fifth in charge’ outside of the laboratory and is happy to let the women in his life take charge. He confesses to “battling a German’s love for cheese and pork” and loves to cook, with Neil Perry’s ‘Balance & Harmony’ cookbook the latest source of culinary inspiration.
And when there is time to take a much-deserved break from his inspirational work for MS, the Butzkueven family pack up and head to an isolated spot in East Gippsland Victoria to enjoy the simple pleasures of camping and hiking.
Associate Professor Butzkueven’s passion for his research into MS is because of the people with MS. “It’s a great privilege to have met so many and to have walked with them for a while. I detest the damage that an illness like MS wreaks on so many people’s lives. But I am noticing that medical science is starting to do a lot better, with new and effective drugs being developed and entering clinical practice. This proves that research is worthwhile.”
“Helmut is a top clinician and terrific researcher – with this research he is fast-tracking our efforts to eventually solve MS,” says Executive Director MS Research Australia, Jeremy Wright.
“Professor John Prineas is both a treasured resource and an inspiration to all involved in the investigation of MS”, said Professor Bill Carroll, Chairman of MS Research Australia’s Research Review Board and Research Management Council.
Professor Prineas was the 2009 winner of the Multiple Sclerosis International Federation’s (MSIF) prestigious biennial Charcot Award for a lifetime achievement in research into the understanding or treatment of multiple sclerosis.
Professor Prineas was selected from an outstanding field of candidates by an international panel of experts from MSIF’s International Medical and Scientific Board, chaired by Professor Alan Thompson.
“The Charcot Award recognizes a life-time contribution to the world of MS and there could be no more deserving recipient,” said Professor Thompson. “John Prineas has made a unique contribution to our understanding of the pathology of multiple sclerosis – over a number of decades, collaborating with colleagues on a truly global scale.”
Professor Prineas graduated in Medicine with honours from the University of Sydney in 1958 and his outstanding career has spanned three continents. He is currently an Honorary Professor in the Department of Medicine at the University of Sydney and a Visiting Professor at the Albert Einstein College of Medicine, New York. His research activities throughout have been directed at understanding the pathogenesis of peripheral and central demyelinating diseases.
As well as the Charcot Award, Professor Prineas’ work has been recognized by a number of other national and international awards including awards from the American Association of Neuropathologists (Weil Award, Moore Award) and the American Neurological Association (Dystel Prize).
The Charcot Award recognizes a life-time of outstanding contribution to MS research, Professor Prineas having been at the forefront of neuropathology in MS. His recent findings of sick and dying cells in the early stages of MS, prior to the autoimmune response, have revolutionized the world-wide understanding of the disease, providing hope for new therapies which include the potential to repair the neural damage.
“These are especially interesting times for the many investigators currently studying tissue changes in the brain and spinal cord in multiple sclerosis,” said Professor John Prineas. “Because of the multitude of new and unexpected findings that have been reported in recent years, we are now in the process of re-writing the basis of our understanding of the nature of tissue injury and repair in the disease.”
“The MSIF Charcot Award for 2009 honours not only my contribution to a particular body of work, and for this I am most grateful, but also the efforts of colleagues with whom I have worked for many years, our patients, and the universities, MS societies and other institutions that have supported this work.”
Professor Prineas is the first Australian to win this prestigious Award and is the recipient of a Project Grant, along with Dr Michael Barnett and Dr Ben Crussett, in the Trish Foundation’s current round of funding.
“Our research funds are certainly in very capable hands,” said Trish Foundation Chairman Carol Langsford.
“Professor Prineas is now presenting information that is changing the course of MS research and he is presenting it in ways that are both profound and inspirational,” said Jeremy Wright, Executive Director of MS Research Australia.
The Trish Foundation is very proud and honoured to be funding such a distinguished and eminent scientist.
Since graduating from the University of Melbourne in December 2000 with a BSc (Hons, First Class), the career of Dr Ben Emery, has gone from strength to strength.
Dr Emery’s Postgraduate Research Scholarship, commencing 2001, was wholly funded by the National Health and Medical Research Council, which only funds the highest calibre research projects and in 2004 Dr Emery was awarded the Young Investigators Prize at the Progress in MS Research Meeting in Melbourne.
Stanford University in the US offered Dr Emery a Postdoctoral position in the Department of Neurobiology commencing 2005, a position supported by a NHMRC CJ Martin fellowship.
“From a work perspective, a definite highlight of my time in the US was the opportunity to work with Professor Ben Barres at Stanford University” says Dr Emery. “Ben Barres is an incredibly tireless and vibrant scientist, and I think much of the current resurgence of research on glia (the “supporting” cells in the brain, including the myelin-forming oligodendrocytes) can be attributed to his passion for these cells over the past two decades.”
“During my time in his lab Ben really gave me the free range and encouragement to follow up on my research interests, and the result was the discovery of a gene that is instrumental in coordinating the myelination process. Through Ben’s lab I was also involved in the Myelin Repair Foundation, a US foundation funding and encouraging collaborations between laboratories with an interest in myelin repair. Through this I was introduced to a lot of other great teams and investigators who I had previously only known by reputation.”
Australian MS research is very fortunate that Dr Emery, who says he thinks he was always drawn to neurobiology research with relevance to human conditions, has returned home.
“We are lucky to have a person of the calibre of Ben Emery devoting his considerable intellect to multiple sclerosis related research. I have every confidence that his work will ultimately be a key factor in improving the lives of people with multiple sclerosis,” says Professor Trevor Kilpatrick.
The Trish Foundation is funding Dr Emery’s current research, “Understanding the events that control central nervous system myelination” at Howard Florey Institute Melbourne.
Dr Emery says that one of the contributing factors to disease progression in MS is the fact that remyelination (myelin repair) becomes less efficient as the disease progresses.
“My research is based on trying to understand the signals that normally drive the myelination process,” says Dr Emery. “This includes both the signals that nerve cells provide to oligodendrocytes (the cells that produce myelin), and the signaling pathways within the oligodendrocytes that allow them to coordinate the cellular changes needed to generate myelin.”
“Generally my research starts off identifying signals that modulate myelination during development in the mouse, and then moves into testing these signals in mouse models of myelin repair. I hope that by fully understanding the myelination process we will be able to develop treatments designed to recreate an environment that promotes remyelination in MS. These treatments could then complement the current therapies that target the immune system.”
Life for Ben Emery, husband and father of a daughter almost two, away from the lab is anything but dull. He says he functions much better with some “decompression” time! This has ranged from rock climbing, sea kayaking and spending five days climbing El Capitan, a 900 metre high rock face in Yosemite in the US to bushwalking in Tasmania and the Victorian alps and cross-country skiing, rock climbing and kayaking back home in Australia.
As the author or co-author of 12 publications, as well as oral and poster presentations at 18 conferences, one wonders how Dr Emery manages to fit so much into each of his very busy and productive days.
Dr Emery says most of his contact with people with MS has come about since he developed his research interests through groups such as the MS Society and the Myelin Repair Foundation in the US.
“Meeting and talking with these people has definitely helped put my research into a human context for me and sustain my interest in it,” says Dr Emery. “I have also known researchers in the field who have close family members with MS – it’s clearly a powerful motivator.”
“Once again the Trish Foundation is backing a winner in funding this outstanding and inspiring young researcher,” says Jeremy Wright, Executive Director MS Research Australia.
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