IHBI Advances March 2016 Edition 25

March 2016 edition 25

ihbi

Institute of Health and Biomedical Innovation

IN THIS ISSUE

ADVANCES Multi-faceted approach to counter hay fever allergies Bid to use native plants for infections and diseases Research push uses implant in bid to stop inflamed mouth Targeting a protein involved in aggressive prostate cancer Global approach needed to unlock migraine complexity Executive Director’s report

IHBI research fellow Dr Ronald Schroeter

Collaboration with industry to develop in-car technology addressing risky driving Researchers in industry and academia are combining their expertise in a collaboration that aims to develop in-car technology to address risky driving behaviour and reduce road deaths and injuries. At the centre of the collaboration is IHBI research fellow Dr Ronald Schroeter.

Dr Schroeter argues risky behaviour is often the result of drivers being under-stimulated. Drivers may take risks by seeking external stimuli, for example through mobile phone use, or set themselves challenges such as speeding, rapid lane changes or tailgating.

ROAD CRASHES Since record keeping started in 1925, there have been more than 185 000 deaths on Australia’s roads.

Road deaths per year have fallen from 3798 in 1970 to 1209 in 2015.

Figures increased from 1155 in 2014 to 1209 in 2015.

DRIVER DISTRACTION One of Queensland Police’s fatal five, along with speeding, drink and drug driving, fatigue and failure to wear a seatbelt.

A contributing factor for about 22 per cent of car crashes.

Almost 80 per cent of crashes and 65 per cent of near-crashes involve some form of driver inattention within three seconds before the event.

SPEEDING A major cause of fatalities on Queensland roads.

Increases the risk of crashing but also the severity of injuries resulting from a crash.

HEAD-UP DISPLAYS A transparent display that presents data without requiring drivers to look away from their usual viewpoints.

Initially developed for military aviation to display airspeed, altitude, a horizon line, heading, turn/bank and slip/skid indicators.

Now installed in luxury cars and available as an after-market option.

Such behaviours and distractions are major causes of more than a million deaths and 50 million serious injuries around the world each year. The cost of road crashes for the Australian society is estimated at $27 billion per year.

Dr Schroeter is working with colleagues at IHBI’s Centre for Accident Research and Road Safety – Queensland (CARRS-Q) and Honda Research Institute in the US to take a new approach to prevention. The focus will be on the time in the car before risk-taking occurs.

“The approach is to understand the psychological and social motivators of risky behaviours and make safe driving more engaging so drivers will take less risk,” Dr Schroeter says.

Key to the research will be determining how to keep drivers engaged and influence behaviour using visual cues projected onto the windscreen in 3D using Honda’s cutting-edge head-up display prototype.

Honda Research Institute is working on installation of a prototype of a 3D augmented reality application across a windscreen in a drivable car. It builds on present technology that provides visual information and situation awareness without drivers taking their eyes off the road.

“The application aims to provide visual stimulus to the driver without causing distraction. Instead, it aims to redirect attention and engagement towards the primary task – driving.”

IHBI researchers will use a simulator study to measure gaze patterns and eye tracking, including fixation on hazards and response times, to evaluate the application.

The studies will use IHBI’s advanced driving simulator, incorporating a life-size car mounted on a motion platform that

can move and twist in three dimensions. A driver in the simulator is immersed in a virtual environment including a 180 degree front field of view, simulated rear view mirror images, surround sound for engine and environment noise, real car cabin and simulated vehicle motion.

The simulator provides an opportunity to study driver behaviour in different conditions, with a high degree of realism, but free of crash risk. A driving scenario can be created to select specifications and enable researchers to observe, challenge and record the driver’s reactions and skills with accuracy.

The research team will establish innovative methodologies on closed road circuits to evaluate the benefits of a 3D head-up display in the real world, with outcomes informing visual design principles for head-up displays, such as optimum size, contrast, colours, movement and timing.

The QUT team includes IHBI professors Andry Rakotonirainy, with expertise in road safety and context-aware systems, and Joanne Wood, with skills in vision and driving; and Associate Professor Daniel Johnson, with experience in human-computer interactions.

Dr Schroeter’s research will be conducted at CARRS–Q with the support of a $300 000 Australian Research Council Linkage Project grant.

“At CARRS-Q, we have long-term partnerships with government and industry bodies in many countries to educate, shape public debate and influence policymakers in road safety. We appreciate the enormous human, economic and social costs resulting from road crashes. The hope is that we can use the latest technology to positively impact on this, address risky driving behaviour and reduce road deaths and injuries.”

Multi-faceted approach to counter hay fever allergies An understanding among researchers that grass pollen allergens are different depending on climate and environment is coupled with a need for more effective tools for diagnosis, treatment, vaccine development and air monitoring. The focus is on subtropical grass pollens found in much of Queensland, meaning IHBI is ideally placed to lead research.

Associate Professor Janet Davies is leading IHBI research that distinguishes between pollen allergens from temperate and subtropical grasses. The distinction is important, given most available allergen treatments target allergies to temperate grass pollens and are less effective when it comes to subtropical variants.

Associate Professor Davies joined IHBI last year, bringing a wealth of skills and expertise in antigen-antibody interactions and a track record of collaborating with industry. Collaborators include allergy diagnosis leaders ThermoScientific in Sweden, treatment experts Stallergenes in France and immunopathology service provider Sullivan Nicolaides Pathology in Australia.

Research that targets subtropical grass pollen allergen components has the potential to reduce the burden of disease in regions in Australia, Asia, Africa and America.

Her work towards developing better treatments for the subtropical Bahia and Johnson grass pollen has support from the National Foundation of Medical Research Innovation.

Grass pollens are a major cause of hay fever and a trigger for allergic asthma. Hay fever, also called allergic rhinitis, affects up to 500 million people worldwide, including 3 million in Australia.

The new subtropical allergy treatment Associate Professor Davies is developing will be a therapy that modulates the allergic immune response to induce tolerance to subtropical grass pollen allergens.

HAY FEVER

At the core of the research are the antibody immunoglobulin E (IgE) that triggers allergic reactions and white blood cells that drive underlying allergic responses. Associate Professor Davies’ group has shown that patient IgE recognises differences between allergens of subtropical and temperate grass pollen.

Also called allergic rhinitis.

Affects up to 500 million people worldwide, including 3 million in Australia.

Co-exists with other chronic allergic diseases such as asthma and eczema.

Can significantly affect a person’s quality of life.

Pollens causing an allergic reaction cannot generally be avoided outside.

Associate Professor Davies has discovered the key allergen components in pollen from subtropical grasses and used the knowledge to design a diagnostic test that is ready for commercial development.

TREATMENT While many people can manage hay fever with over-the-counter antihistamines and nasal sprays, for about a third of people that approach is inadequate.

Drops and tablets for treating hay fever and asthma resulting from allergies to temperate grass pollens have been standardised.

Treatments for pollens are less effective in targeting pollens from subtropical grasses that are abundant in Queensland.

Pharmacy wholesale purchases for antihistamines and nasal steroids doubled from 2001 to 2010 to $226 million.

“The test can identify people who need, and would respond to, better subtropical grass pollen allergy vaccines,” she says.

“An additional need is to monitor allergens in the air so people can manage medication use and minimise environmental exposure.”

Associate Professor Janet Davies

Another element of the research Associate Professor Davies conducts involves understanding the variability in grass pollen seasons across Australia’s vast regions and between years.

A static grass pollen calendar, typically indicating month by month pollen levels based on averages and patterns, are at best of limited use and at worst misleading. Instead, Associate Professor Davies advocates forecasting based on grass growing and flowering times and weather factors. Recent studies of pollen exposure involved Associate Professor Davies collaborating with peers from across Australia, New Zealand, the US and Europe.

“Australia is one of the few developed countries without a national pollen monitoring program. While we are a nation with one of the highest hay fever burdens, little is known about the timing and levels of exposure to airborne grass pollen across Australian cities.”

Associate Professor Davies leads the Australian Pollen Allergen Partnership that aims to provide up-to-date pollen information and forecasts to patients and doctors in major cities. The project has support from the Allergy and Immunology Foundation of Australia and co-sponsorship from partners Asthma Australia and Stallergenes Australia.

“It is important to have this information available. Allergic diseases in Australia have a high economic burden, costing $7.8 billion each year, including $1.2 billion in direct medical expenses.”

Bid to use native plants for infections and diseases Australian native plants are at the centre of a collaboration between IHBI and industry partner Health Focus Products Australia that aims to develop therapeutics for infections and diseases.

The partnership shows great potential in improving the lives of people with Alzheimer’s disease, Parkinson’s disease and chronic and antibiotic-resistant wounds.

Dr Trudi Collet

IHBI’s Dr Trudi Collet will use her expertise in wound healing, immunology, pharmacology, complementary medicines and molecular microbiology to conduct research into the compounds found in the native plants.

The research will be split into three projects, with two native plants the focus for use as antimicrobials for treating the antibiotic-resistant infection MRSA. Another three native plants will be studied for use in wound healing and antimicrobial and anti-inflammatory properties. The third project will investigate a compound derived from the leaves of a native plant for treating neurodegenerative diseases Alzheimer’s and Parkinson’s.

Dr Collet says the potential therapeutic value of compounds derived from plants is now more readily accepted, but much CHRONIC WOUNDS A wound that does not heal in an orderly set of stages and in a predictable amount of time.

Wounds that do not heal within three months are often considered chronic.

433 000 Australians diagnosed each year.

Incidence expected to rise as the population ages.

Cause severe emotional and physical stress for people.

Create a significant financial burden, estimated at $2.6 billion each year in Australia.

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Health Focus Products Australia will provide more than $1 million to support the research, as well as providing expertise in the development of a marketable product. The funding also incorporates successful grants from the Federal Government’s Innovation Connections scheme.

“It is exciting,” Dr Collet says. “We are making important scientific discoveries. For example, after only four weeks of work, we have discovered that crude extracts obtained from an Australian native plant shows significant antimicrobial activity against MRSA strains and other common wound-colonising bacteria.

“Given the increasing incidence of antibiotic resistance coupled with the high prevalence of MRSA-infected wounds, the potential benefits are substantial. A novel broad-spectrum antibiotic would have a global application, since present therapies to clear infections are limited.”

Similarly, very few medicines capable of significantly promoting wound repair are commercially available. Dr Collet aims to use compounds from three native plants to overcome the high incidence of chronic non-healing wounds, often exacerbated by poor circulation, a person’s general ill-health or advanced age.

Risk factors include diabetes, cardiovascular disease and obesity.

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work needs to be done to understand how they can best be used for effective therapeutic treatments.

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“Compounds from the native plants appear to have the ability to enhance proliferation of healthy cells and skin stratification – that is, speeding up wound healing,” Dr Collet says. “It is a way of assisting the body to repair itself.”

The compounds Dr Collet is studying do more than overcome infections and promote skin healing. One compound has the potential to block the breakdown of enzymes in the brain that is associated with degeneration and onset of neurodegenerative diseases.

The compound shows an ability to selectively block the breakdown of both acetyl- and butyryl- cholinesterase to maintain and enhance normal brain function in people with Alzheimer’s disease.

Dr Collet says the research draws on IHBI strengths in tissue repair and regeneration, infectious disease, chronic disease and ageing. It also leverages Health Focus Products Australia’s expertise in product development and industrial-scale therapeutics to ensure the research has a focus on translation and clinical relevance.

“The researchers in my group are mindful their work aims to bridge the gap between science and healthcare. It’s about understanding the properties of native plants and how they can be manufactured by industry to improve people’s lives.”

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Research push uses implant in bid to stop inflamed mouth Nearly a quarter of Australian adults have periodontitis, an inflammation that can degrade specialised supportive tissue and ultimately lead to a loss of teeth. IHBI’s Dr Yinghong Zhou is using new Federal Government funding to develop a novel implant to enhance tissue regeneration and secure the teeth.

Dr Yinghong Zhou

Dr Zhou received a National Health and Medical Research Council (NHMRC) Early Career Peter Doherty – Australian Biomedical Fellowship late last year to support her research into periodontal regeneration. The funding is a major achievement given she completed her PhD studies under IHBI bone and tissue engineering researcher Professor Yin Xiao less than two years ago.

PERIODONTITIS An inflammatory disease of the periodontium, specialised tissue that surrounds and supports teeth, caused by the formation of a bacterial biofilm and leading to tissue destruction. It is estimated that nearly a quarter of Australian adults have periodontitis.

SYMPTOMS Gingival inflammation and bone destruction are largely painless. Symptoms may include: •

Redness or bleeding of gums while brushing teeth, using dental floss or biting into hard food.

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Recurring gum swelling.

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Spitting out blood after brushing teeth.

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Bad breath, and a persistent metallic taste in the mouth.

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Gingival recession, resulting in apparent lengthening of teeth.

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Deep pockets between the teeth and the gums.

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Loose teeth, in the later stages.

PREVENTION Measures include: •

Brushing properly at least twice daily, including underneath the gum-line.

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Flossing daily.

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Using an antiseptic mouthwash.

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Regular dental check-ups and professional teeth cleaning as required.

Dr Zhou will use the funding to determine the role of periodontal ligament cells (PDLCs) in tissue regeneration and their link to signalling cues.

Cell signalling is part of communication governing cellular activities. The ability of cells to perceive and correctly respond to their environment is the basis of development, tissue repair and immunity. Errors in cellular information processing are responsible for diseases such as cancer, autoimmunity and diabetes. By understanding cell signalling, diseases may be treated effectively and artificial tissues may one day be created.

Dr Zhou’s research will use a novel scaffold that can target cell signalling to regenerate periodontal tissues. The aim is to determine its efficacy in encouraging regeneration of tissue damaged through periodontitis. Tissue at risk of damage through periodontitis includes cementum, a calcified layer covering the root of a tooth, periodontal ligament and alveolar bone.

aims to steer the body to form new bone, healthy cementum and signal PDLCs towards regeneration.

“Present treatments have limitations in restoring the periodontium architecture because of the complex structure consisting of soft tissue such as gum and hard tissue such as bone,” she says.

The formation of cementum is the most important event in periodontal regeneration. Filaments from the periodontal ligament insert into cementum and anchor the tooth. In a recent study, Dr Zhou and fellow IHBI researchers showed the cementum is incapable of self-repair or regeneration. Additional research shows regulation of cell signalling mediates cementum regeneration.

Dr Zhou says IHBI is an advantageous place for the work, given its multidisciplinary approach to research, focus on clinical relevance and international links to a network of leaders in their field. She works closely with Professor Xiao, who heads the The scaffold is created using bio-ink and a person’s stem cells Australia-China Centre for Tissue Engineering and Regenerative to form intricate layers that encourage the body’s regenerative Medicine (ACCTERM), has more than 10 years clinical mechanisms. Infusing growth enhancer and a person’s own stem experience and is himself a former recipient of the cells encourages growth of the correct tissue type to repair the Peter Doherty Fellowship. site and overcomes the fear of rejection associated with donated organs or foreign material. The layers will eventually break down “I have met highly-regarded Chinese researchers in the body as new tissue grows to replace it. who collaborate with Professor Xiao through ACCTERM,” Dr Zhou says. “It has enabled me to start building a network Ultimately, Dr Zhou says the research aims to determine of contacts and gain important insights in tissue engineering the efficacy of periodontal therapy in reconstructing a tooth’s and regenerative medicine.” attachment apparatus lost due to periodontitis. The therapy

Targeting a protein involved in aggressive prostrate cancer Prostate cancer is the most common cancer diagnosed in Australia and the third most common cause of cancer death. While treatment is initially effective, benefit is sometimes temporary as prostate tumour cells adapt to survive. IHBI researchers are targeting a specific protein to improve survival rates for men with aggressive forms of the cancer.

PROSTATE CANCER RISK FACTORS Age: The chance of developing it increases with age. The risk of prostate cancer by the age of 75 is one in seven men. By the age of 85, that increases to one in five.

Family history: Risks increase where men have a first degree male relative with prostate cancer. They increase again if more than one male relative has prostate cancer.

Genetics: Changes to genes can increase the risk of prostate cancer being passed from parent to child. Although prostate cancer can’t be inherited, a man can inherit genes that can increase the risk.

Diet and lifestyle: There is some evidence to suggest that environment, lifestyle and a diet high in processed meat or fat can increase the risk.

REDUCING THE RISK There is no evidence protective factors can stop prostate cancer development, but they can improve overall health and possibly reduce the risk.

Diet: Eat nutritious meals.

Exercise: There is some evidence to show that regular exercise can be protective for cancer. Exercise at least 30 minutes a day.

SYMPTOMS Some common symptoms associated with a disordered prostate are: •

difficulty in starting to urinate

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blood in the urine or semen

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discomfort when urinating

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a slow flow of urine that is difficult to stop

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a decreased libido.

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Professor Colleen Nelson

Prostate cancer most commonly proves fatal when the disease develops therapeutic resistance, leading to uncontrolled metastatic tumour growth. Treatment options for men with aggressive forms of prostate cancer are limited. Androgen-axis targeted therapies, such as androgen deprivation therapy and anti-androgen compounds, are the standard treatment for such metastatic prostate cancer.

Researchers working at the Australian Prostate Cancer Research Centre – Queensland (APCRC-Q) have identified a protein found in abundance, or highly expressed, in aggressive and treatment-resistant forms of prostate cancer. They believe targeting the protein represents the best chance of improving treatment efficacy and survival rates.

Working under the leadership of APCRC-Q Executive Director, Professor Colleen Nelson, the researchers aim to characterise the protein’s role in the lethal progression of prostate cancer and to develop a new therapeutic agent to inhibit a cancer cell’s production of the protein. The expectation is that a newly-developed therapy could be used in combination with present treatments.

“The ultimate aim is to translate the findings from the laboratory into the clinic for men with advanced prostate cancer,” Professor Nelson says. “Prostate cancer is the most prevalent non-skin cancer in Australia and causes more than 3000 deaths each year nationally.

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“We collaborate widely with other research institutes, clinicians and industry around Australia and in Canada, Ireland and the US,” she says. “We appreciate the importance of working with the best minds from around the world and looking at the complexity of prostate cancer in a holistic way so we can positively impact on people’s health – and ultimately their lives.”

Supporting the research is a National Health and Medical Research Council (NHMRC) Project Grant of $780 338 that involves IHBI’s Dr Brett Hollier studying the mechanisms that mediate cancer metastasis and input from Professor Martin Gleave at the University of British Columbia in Canada.

The funding adds to APCRC-Q success in securing a $703 541 Development Grant from the NHMRC to work with industry partner company Minomic to develop a prostate cancer diagnostic for early detection.

Prostate cancer occurs when some prostate cells multiply more rapidly than is normal, resulting in a tumour. Prostate cancer cells eventually invade other parts of the body, producing secondary tumours. The process is called metastasis.

Treatment is still possible once the cancer escapes the prostate, but there is presently no cure.

Professor Nelson says the APCRC-Q is based at the Translational Research Institute (TRI) to advance research, promote collaboration and ensure a focus on clinical outcomes.

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Medical research needs to be multi-dimensional to obtain an accurate ‘big picture’ of complex diseases. Migraine research is a perfect example. IHBI Associate Professor Dale Nyholt aims to identify the links between genetic and environmental aspects and their bearing on risk factors and treatment responses.

Associate Professor Nyholt and members of his Statistical and Genomic Epidemiology Laboratory joined IHBI in February 2015, adding capacity in migraine research to that already conducted through the Genomics Research Centre. He collaborates widely with leading researchers from the US, Germany, Austria, the Netherlands and around Australia.

The research conducted around the globe aims to fill the knowledge gap that has prevented development of effective and well-tolerated treatments for migraine. Recent treatment options for acute migraine attacks elicited responses in only 60-70 per cent of people, with at least another 10 per cent reporting mixed results for efficacy and tolerance.

Migraine is one of the most prevalent, disabling, misdiagnosed and misunderstood disorders. The exact causes are unknown.

What makes migraine so complex is the combined effect of genes, environmental factors and their interactions.

The heritability of migraine is about 50 per cent, meaning genes and environment equally contribute to migraine risk for people. Attacks rarely occur spontaneously without environmental triggers, with the most common believed to be stress, sensory triggers such as eyestrain, noise or odours, hunger, lack of sleep, food such as chocolate or cheese, alcohol and weather.

“My research investigates the genomic and environmental causes of migraine,” Associate Professor Nyholt says. “We need a deeper understanding of the patterns and causes of migraine in order to prevent and treat attacks and identify new targets for therapeutic therapy.”

A focus of the research is identifying subgroups of people with migraine that are similar in symptoms and underlying biology.

MIGRAINE Characterised by recurring attacks of severe pulsating head pain.

Associated symptoms include nausea, vomiting and changes in mood or energy levels.

Nearly a quarter of people will have recurring attacks during their life.

Impacts up to 33 per cent of women and 13 per cent of men.

The result of combined effect of genes, environmental factors and their interactions.

Majority of attacks start at a young age, between five and 25 years.

EXECUTIVE DIRECTOR’S REPORT

In two-thirds of people, attacks will continue for many decades, often into very old age.

Another research strand will characterise genetic risk factors, environmental triggers, traits linked with other medical conditions and treatment response. “We know migraine co-occurs with several disorders including anxiety, asthma, depression, endometriosis, epilepsy, obesity and substance abuse,” Associate Professor Nyholt says. “That may affect treatment adherence, increase risk of medication overuse and transform migraine to a more chronic form. That complicates treatment for a subgroup of people with migraine.”

Innovation is an important element in research at IHBI and a basis for much of the thinking, planning and team-building.

Innovation is the process of translating an idea or invention into goods or services that create value or for which customers will pay. To be considered an innovation, an idea must be replicable at an economical cost and must satisfy a specific need.

Similarly, Dr Trudi Collet is working closely with industry partner Health Focus Products Australia. The collaboration aims to develop therapeutics derived from native plants for treating infections and diseases, using Federal Government support and showing great potential for improving the lives of people with a range of medical ailments.

In health and biomedical research, innovation needs to be closely coupled with translation and commercialisation—both terms that describe the process of moving research from the lab to a medical product, therapeutic or service to benefit people around the world.

Partner company Minomic is working with Professor Colleen Nelson on developing a prostate cancer diagnostic for early detection. The work involves collaborations with oncologists; input from researchers and industry in Australia and Canada; and a successful bid for funding from the National Health and Medical Research Council.

It is pleasing to see IHBI researchers being innovative in translating their research using competitive national funding, industry partners, clinical collaborators and the latest technology.

Dr Ronald Schroeter incorporates much of this in his research into combating risky driving behaviour and reducing road deaths and injuries. Dr Schroeter is an early-career researcher who is still establishing his credentials and building a collaborative network, but is already attracting attention and competitive funding while working with Honda on a 3D augmented reality application for next-generation cars.

Industry leaders in diagnostics, treatment and service provision are also integral to the research of Associate Professor Janet Davies. Her research aims to understand pollens and triggers for hay fever and allergic asthma and use the insight to develop diagnosis, treatment, vaccine and air monitoring tools.

To understand migraine, a complex disease that is often misdiagnosed and misunderstood, Associate Professor Dale Nyholt is collaborating with experts from the US, Germany, Austria, the Netherlands and around Australia and has a

Data gathered from studies into the migraine subgroups and characterisation of genetic and environmental factors will enable Associate Professor Nyholt to better understand the interaction between genetic and environmental aspects and their bearing on risk factors and treatment responses.

“The research takes a multi-dimensional approach so that we have the best chance of developing a treatment regime that will prove effective for a subgroup of people with migraine,” he says. “For example, identifying people most at risk of co-occurring chronic migraine and depression due to medication overuse or identifying subgroups of people for whom particular treatments may be most effective.”

Assisting the research is Associate Professor Nyholt’s leading role in EUROHEADPAIN, an international collaboration based at Leiden University Medical Centre in the Netherlands that aims to identify and investigate biomarkers for migraine. The biomarkers point to the presence of migraine, or migraine susceptibility, and may prove to have a role in diagnosis and treatment.

EUROHEADPAIN was awarded €6 million to investigate migraine mechanism and treatment, recognising its prevalence, disability, complexity and global socio-economic burden.

leading role in EUROHEADPAIN. He aims to identify links between genetic and environmental aspects and their bearing on migraine treatment and treatment response.

Collaboration with some of the world’s best minds through the Australia-China Centre for Tissue Engineering and Regenerative Medicine and national competitive funding is assisting Dr Yinghong Zhou in her research. She is developing a novel implant to enhance tissue regeneration and secure teeth in people with periodontitis.

What each of the IHBI research projects has in common is a novel and encompassing approach to a medical problem.

Such an approach not only takes into account the need to answer questions related to the underlying biologic, chemical or material science but the way to effectively develop treatments or therapeutics that can be replicated in the hospital or clinic; or that industry can economically manufacture. That is innovative thinking.

Professor Lyn Griffiths Executive Director, IHBI

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