Success stories and Research Office newsletter
World first MS biomarker discovery lead by our researchers
Tiny changes, huge repercussions
For neuroscientist Professor Gilles Guillemin, determining minute changes in specific chemical pathways within the brain is key to unlocking the progression of neurodegenerative diseases like multiple sclerosis (MS), Alzheimer's disease and Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's in USA.
“We specifically look at a biochemical pathway that uses a chemical called tryptophan which is known to be involved in brain inflammation,” says Professor Guillemin.
Guillemin, who has been working in the field of Neuroimmunology for more than 24 years and in the field of tryptophan metabolism for 20 years, has shown through research that the tryptophan pathway is integral in many neurodegenerative diseases. These results have been particularly useful in the advancement of disease biomarkers, including the development of the first prognosis biomarker for MS which Guillemin and Dr Edwin (Chai) Lim recently announced in a paper published in the journal Scientific Reports.
“We have developed a biomarker test which will allow clinicians to determine which type of MS a patient has with 85-91 per cent accuracy, negating the need for patients to have to undergo an array of expensive tests to get the same answer,” he explains. “The new results show that a blood test could greatly simplify and speed up this process, which is significant for patients because it will allow their clinicians to quickly and simply make a prognosis and adapt their MS treatment more accurately and rapidly.”
Over the years, a number of key organisations have collectively provided around $1 million in funding to advance the research, including start-up and ongoing funding from MS Research Australia, an Australian Research Council fellowship, as well as grants from the National Health and Medical Research Council, the Ramaciotti Foundation, the Deb Bailey Foundation and Macquarie University.
More than 12 years later, the researchers are now working on commercialising the biomarker so that clinical labs around the world can aid MS patients in receiving a quick prognosis.
Mentoring a bright young star
Over the past few years Professor Guillemin has been working with Dr Lim, an emerging young analytical biochemist with highly specialised skills when it comes to investigating tryptophan metabolism. With only five years of postdoctoral experience, he already holds two patents and is a technical consultant with Michigan State University in the USA.
Working within the Guillemin laboratory, Lim is aiming to generate large amounts of clinical data for the biochemical pathway that uses tryptophan, called the kynurenine pathway, for various diseases.
“This will allow us to perform a disease wide analysis to fully delineate the role of the tryptophan processing pathway in a number of brain conditions,” says Lim.
Having published 21 peer reviewed research articles in the last three years relating to this pathway, Lim’s enthusiasm to learn more about the nuances of tryptophan metabolism led to the discovery of six compounds found to be critical in determining specific types of MS, allowing the development of the world’s first MS biomarker.
Collaborate to completion
Guillemin is currently engaged in 34 active collaborations with researchers from around the globe, including scientists from Australia, France, Spain, Chile, Brazil, USA, South Africa, Oman, Kuwait and China. For the biomarker research alone, Guillemin and Lim have worked with a large and accomplished group of researchers, including Macquarie University’s Associate Professor Ayse Bilgin, St Vincent’s Centre for Applied Medical Research Centre’s Professor Bruce Brew, Menzies Research Institute Tasmania’s Professor Bruce Taylor, Ms Sonia Bustamante from the University of New South Wales, and international collaborator, Dr Alban Bessede from ImmuSmol in France.
“We are now in the process of developing a new MS prognostic kit in collaboration with Dr Alban Bessede’s laboratory in France. To do this, we needed to develop specific and sensitive set of antibodies that are able to detect the small molecules identified as biomarkers,” Guillemin explains. “This is extremely challenging and only a few companies in the world have this expertise, ImmuSmol being one of them.”
Over the last 18 months, the researchers have been developing a commercial test kit, with the support of the Australian company Dianti MS Pty. Ltd., which they are aiming to have available to Australian pathology clinics within two years, and available to pathology labs worldwide soon after.
A simple test
The clinical MS biomarker test kit will enable patients to receive a prognosis within 24-48 hours, allowing them to start an adapted treatment regimen earlier and limiting the autoimmune damages in the brain and spinal cord caused by MS.
“This has the clear capacity to be the first ever blood biomarker for the prognosis of MS, and in doing so will meet one of the real unmet needs in the clinical management of MS,” says Dr Matthew Miles, CEO of MS Research Australia. “We have been excited to be part of the translation of this initially fundamental research into a potential clinical test.”
Currently, most existing MS therapies only work for the relapsing remitting subtype of MS, whereas some new treatments on the market actually benefit those with the secondary progressive subtype of MS. Guillemin says that a quick prognosis result from the clinical test kit will allow clinicians to quickly gauge when to stop or change MS therapies, which is critical when it comes to sparing patients the side effects and cost of unnecessary treatments.
“The results of the recent research identify biomarker components that could be potential therapeutic targets for MS and could also be used to assess the response of new drugs for the treatment of MS in clinical trials. Future research will need to look at ways to rectify the abnormal levels of these components in MS patients in order to potentially delay or halt progression of a patient’s condition,” concludes Guillemin.
Past Success Stories
Mind mapping - June 2017
For entomologist Associate Professor Andrew Barron, his research holy grail is finding out what insects think – and then creating a neurobiological model that displays the passage of those thoughts as they spark across the neural circuitry.
“I don’t believe that consciousness is outside the capacity of neuroscientific examination,” he says.
Barron, who started his research career working on flies at the University of Cambridge, decided to switch his focus to honeybees after completing his PhD, driven by worldwide concerns over pollinator decline and a fascination with how minds work. These interests coalesced around an initiative to model the insect brain.
“Although their brains are minute, bees exhibit astonishingly complex behaviour,” he explains. “This means when it comes to understanding what drives animal behaviour, insects and bees have a real advantage over other animals."
In 2001 he was awarded a Fulbright Scholarship and spent a year working with Professor Gene Robinson from the Carl Woese Institute for Genomic Biology at the University of Illinois.
More than 15 years later, Barron and Robinson continue to collaborate, recently publishing an article in Science that demonstrated that instinctive behaviours – such as honeybees’ inherent knowledge of how to communicate the location of food sources in their environment to their colony using movement and sound – may evolve from the process of learning until they eventually become hard-wired into the DNA.
They showed that both learning and instinctive behaviours are regulated by the same cellular and molecular mechanisms, adding to the growing body of research in the exciting new field known as epigenetics, and proposed the first general model of how instincts can evolve.
From mentee to mentor
Over the past year, Barron has been on the other side of the Fulbright Scholarship relationship, mentoring PhD student and Fulbright scholarship holder Brian Entler.
“This is a competitive award and the students who get through are exceptional,” Barron says. “Brian was a highly motivated, dynamic character who took advantage of any opportunity to increase his skills, becoming involved in everything that was happening in the lab.
“As a result of his enthusiasm, and the work he undertook while he was at Macquarie, he contributed to three papers that are yet to be published.
“He has returned to the US to continue his studies, but while he was here his passion and enthusiasm energised and helped lift the research performance of the whole team.”
In 2009, research that involved stimulating the reward system of bees using cocaine attracted the attention of the world’s media.
Barron found surprising similarities between the ways bees and humans react, with the drug altering affected bees’ judgement, stimulating their behaviour and making them overestimate the value of the pollen and nectar they found.
“The cocaine triggered the release of octopamine, which has a similar effect on the brain to dopamine in humans. It caused the bees to dance more vigorously than their finds warranted,” he explains, adding that the research revealed new insights into how brains react to drugs of abuse on a molecular basis.
While much of Barron’s work focuses on creating a functional model of the honeybee brain, he has also written for Nature about the implications of media sensationalisation of research on animal sexual behaviour, particularly when it comes to relationships between animals of the same sex.
Making stressed colonies resilient
Another research avenue Barron is focusing on is the survival of bee populations worldwide, which have been decimated by Colony Collapse Disorder – a phenomenon in which entire bee colonies suddenly disappear without trace.
During research that tracked bees using miniature radio tags, Barron and colleagues found that stress, in the form of parasites, pathogens and pesticides, may be the problem.
“Bees from stressed colonies start foraging too young, with lower foraging success rates and increased risk of death.”
Modelling showed it doesn’t take much to tip the balance from a healthy, productive hive to one in mortal decline: decreased food for the colony and increased forager mortality led to rapid colony collapse.
But the news wasn’t all bad, with the researchers suggesting that by simply supplementary feeding hives during times of stress could help stave off colony collapse.
Barron says that all of his work is connected: “As our knowledge of bee biology has increased, so too has our understanding of how to improve colony function and health”.
It all comes back to the brain
While insect brains and human brains could not look more different, they have structures that do the same thing. But because of the mammalian brain’s complexity, creating a model of its circuitry remains out of reach for researchers.
In 2015, Barron was awarded an ARC Future Fellowship to develop computational and mathematical models of the honeybee brain. He is currently mapping their neural networks and relating function to network activity within the brain.
“The small size of the bee brain constrains the model, meaning that only so many connections between neurons (for processing information about place, smell and colour) are possible. Once we know how they connect we can create a proper circuit model,” he says.
“Even though they’re small, they are still able to solve complex problems. For all bees, foraging on flowers is a hard life. It is energetically and cognitively demanding; bees have to travel large distances to collect pollen and nectar from sometimes hard-to-find flowers, and return it all to the nest without running out of power, getting lost or dying.
“To do this they need finely tuned senses, spatial awareness, learning and memory, and do it with a brain of just a few cubic millimetres.”
Applications for 2018 Fulbright Scholarships are currently open and will close 1 August 2017.
Philanthropic grant success: Pocket Rockets - May 2017
Meet Dr Carol Newall from the Department of Educational Studies, Faculty of Human Sciences (this is not her pictured!). She is a tenacious go-getter and an impressive academic. Dr Newall understands what philanthropic foundations want from their granting: in-depth engagement and clear demonstration on how their funding will change the world for the better. She has been successful in receiving grants from many different avenues.
In 2015, Dr Newall defied the odds and secured funding from the Ian Potter Foundation, one of Australia’s largest private foundations, who supports a variety of areas including arts, community wellbeing, education, and the environment amongst others (last financial year they gave out over $36 million to 267 projects). In 2015/16, only 10% of applications in their Education stream were successful, so Dr Newall is a proven superstar. The funding was for a small pilot program for Pocket Rockets, an innovative STEM workshop for children aged 4-6 years, in collaboration with Dr Kate Highfield at Swinburne University.
With the help of the Office of Advancement, Dr Newall has successfully managed the relationship with the funder, including:
- Managing the funds so well that she was able to undertake 2 extra free workshops for children in remote areas (above and beyond what the Foundation expected)
- Inviting the Foundation along to the workshops and ensuring they have been kept up to date where appropriate
The way that Dr Newall has managed this relationship is best-practice. She has treated them as a partnership, rather than as a transactional relationship. She has ensured that they are ‘inside the tent’ rather than keeping them at arm’s length. This will have done wonders in bolstering Macquarie’s reputation with the Foundation, which can only benefit all of our future applications.
We have also been able to leverage Dr Newall’s program. Through connections in the Office of Advancement, we have met with the Head of the St George Foundation (the bank’s philanthropic arm) and received their first ever donation to an Australian University. This is unheard of!
Because of Dr Newall’s persistence and understanding of the philanthropic landscape, philanthropic funding for her work continues to grow.
Faculty of Arts working with Optus for positive social impact through technology - April 2017
Dr Rowan Tulloch from the Department of Media, Music, Communication and Cultural Studies was funded by the Optus Future Makers for his pitch ‘The Game Change’.
The inaugural Optus Future Makers program fosters digital innovation that will impact how we socially engage. A tense pitching process to a panel of experts by eleven emerging digital influencers took place in front of an audience at the Optus Campus in Sydney.
The innovators had just 180 seconds each (with no notes or power point slides) to secure their share of the $300,000 funding pot and six walked away with enough financial backing to bring their ideas to life.
Rowan won $50,000 to help make his innovative idea a reality. Rowan said “it was so far out of my academic comfort zone, but it must have gone well because they funded me to the full amount”. The Game Change is software that helps university and school teachers gamify their classrooms to better engage and motivate students. The software is also designed to assist students who are marginalised by traditional teaching practices. Through the Future Makers program, Rowan found his collaborator, Epiphany Games, and has been able to expand the scope and enhance the timeline of his original proposal, and to hopefully bring The Game Change app to market.
Paul O’Sullivan, Future Makers Judge and Optus Chairman, said, “This program is about helping Australia’s innovators to make a positive social impact through the use of technology. We know how important technology is in people’s daily lives, and with Future Makers we are specifically targeting projects that will benefit marginalised and vulnerable youth.”
“I think the main thing that gamification can give us as teachers is the possibility to open up a dialogue with students and to help guide them into the practices that we take for granted,” Rowan says.
For further details from Rowan himself, listen to the PioneeringMinds podcast.