Otago scientists secure more than $26m for health research

Professor Michael Baker.

University of Otago, Wellington infectious diseases expert Professor Michael Baker has received almost $5 million from the Health Research Council for a programme investigating the connection between infectious diseases and long-term conditions, something he was planning well prior to the outbreak of Covid-19.

This new programme is called SYMBIOTIC: Syndemic Management of the Biology and Treatment of Infections and Chronic conditions. Professor Baker explains the central idea is that infectious diseases and serious long-term conditions like chronic lung disease and diabetes tend to occur together, known as “syndemics”.

“The programme was written in 2019 but the ideas are very relevant to our current response to Covid-19 where the risks of infection and poor outcomes are strongly influenced by the presence of chronic conditions and poverty,” Professor Baker says.

“A major goal of the programme is to better understand the two-way relationship between acute and long-term conditions to improve health and equity in New Zealand.”

In total, the Health Research Council this year awarded $71.58 million to 47 research projects nationally with the University of Otago receiving $26,557,603.

SYMBIOTIC lead researcher Dr Amanda Kvalsvig says the programme will work in partnership with communities, healthcare providers, Māori health providers and policymakers to create practical, effective solutions to break syndemic cycles in a bid to improve health and equity.

“We need a transformational model that can address these complex health issues as a whole, instead of the fragmented approaches that have been used until now.”

Finding the best screening and treatment strategy to eliminate a chronic stomach infection (Helicobacter pylori) to prevent stomach cancer is just one of the areas to be investigated as well as reducing unnecessary use of antibiotics in childhood to prevent long-term conditions like diabetes, inflammatory bowel disease and attention deficit hyperactivity disorder that may be linked to antibiotic use.

A senior Māori researcher in the group, Anaru Waa, says a key strength of the programme is the potential for innovative solutions that combine syndemic approaches with Māori models of health.

“Grounding the research within Māori experiences will help identify solutions for how infectious diseases and long-term conditions can better be managed by and with Māori communities,” Mr Waa says.

The University of Otago's housing and health research programme He Kāinga Oranga is the other big winner in the latest HRC grants, also set to receive just under $5 million over five years to continue research to maximise the health and wellbeing gains from housing.

Associate Professor Nevil Pierse.

University of Otago, Wellington, Associate Professor Nevil Pierse; Distinguished Professor Philippa Howden-Chapman and a multidisciplinary group including researchers from the universities of Otago, Victoria and Massey, BRNAZ and Motu Economic and Public Policy Research will evaluate and scale up existing housing interventions that are proven to be effective and test a suite of new interventions designed to increase equitable health outcomes and enhance New Zealanders' wellbeing.

Healthy Homes programme co-leader, Associate Professor Pierse, says the research group is very pleased to receive the funding.

“Despite the significant progress made in recent years to improve the quality of New Zealand's homes through subsidised insulation schemes and energy efficient heating, up to 900,000 New Zealand homes remain unhealthy, with low-income renters most at risk.

“New Zealand's poor housing quality, particularly private rental housing, has created a large health burden with 28,000 children and 54,000 adults hospitalised each year for potentially avoidable hospitalisations linked to old, cold, damp and mouldy houses. Most of these affected children come from low-income households with Māori and Pasifika children three and four times over-represented,” he says.

As part of the five-year programme, the research team will work closely with the Ministry of Business, Innovation and Employment to measure the impact that new mandatory Health Homes Standards for rental properties, due to be in place from July next year, are having on housing quality, including indoor temperatures, air quality, physical and mental health and mortality. The standards cover improvements to heating, insulation and ventilation and address issues with moisture ingress and drainage.

University of Otago Deputy Vice-Chancellor, Research and Enterprise, Professor Richard Blaikie, says the extraordinary strengths of health research at Otago is reflected in these results, particularly from groups that work in areas related to infectious diseases and public health, that are so critical in the current environment.

“The breadth of activity is also remarkable and we thank the Health Research Council for their enduring support across all areas relevant to the health and wellbeing of New Zealanders.”

For further information, contact

Professor Michael Baker
University of Otago, Wellington
Email michael.baker@otago.ac.nz

Associate Professor Nevil Pierse
University of Otago, Wellington
Email nevil.pierse@otago.ac.nz

Liane Topham-Kindley
Senior Communications Adviser
Tel +64 3 479 9065
Mob +64 21 279 9065
Email liane.topham-kindley@otago.ac.nz

The successful Otago research projects are outlined below:

Professor Gregory Cook, University of Otago

Unlocking Antimicrobial Tolerance in Bacterial Pathogens to Overcome AMR
36 months, $1,197,343.55

A key component in combatting the global pandemic of antimicrobial resistance is understanding how bacteria become tolerant to antimicrobials. Antimicrobial tolerance has been shown to facilitate the development of bona fide resistance, but the molecular mechanisms underpinning tolerance remain largely unknown. Professor Cook's team has identified a unique signalling system in bacterial pathogens that controls tolerance to all major classes of cell wall antimicrobials. The aim of this study is to determine the structure and function of this signalling system in antimicrobial tolerance to provide a molecular blueprint for drug development.

Professor Catherine Day, University of Otago

Time for destruction - switching immune responses off
36 months, $1,197,433.37

This work will provide fundamental knowledge about the mechanisms by which inflammatory signalling is turned off following viral infection. It will also identify possible molecular targets for chronic inflammation, and explain how immunostimulatory therapies that are being developed to enhance cancer treatments might achieve maximum benefit.

Professor Paul Glue, University of Otago

Ketamine therapy for neurotic disorders: is there a single mechanism?
36 months, $1,438,829.50

Professor Glue's research team will further investigate the use of ketamine as treatment for neurotic disorders. Conventional drugs often target only some of these disorders, taking months for their full effects. About 30 per cent of patients are completely treatment-resistant, with high use of public resources and risk of suicide attempts; but ketamine appears swiftly therapeutic in all – and no-one knows how. Professor Glue's team will, for the first time, assess brain activity and efficacy during ketamine therapy across a wide range of neurotic disorders. The results should produce major theoretical advances and lead to new methods that could revolutionise treatment for patients with this broad group of stress related disorders.

Professor David Grattan, University of Otago

A neural circuit required for maternal adaptation to pregnancy
36 months, $1,199,971.30

Maternal care is critical to the survival of dependent offspring. Professor Grattan's team have described a circuit in the brain that is essential for a mother to look after her offspring. In this project, he and fellow principal investigator Dr Rosie Brown, aim to map the different projections of neurons within this circuit and determine whether different projections are involved in different aspects of maternal care. There is increasing recognition that pregnancy hormones such as prolactin exert significant influence on the maternal brain, and that abnormalities in adaptive responses to these hormones may be associated with perinatal mental illness. This research will provide new insights into the hormonal regulation of maternal behaviour, and how hormones facilitate the development of maternal-infant bonds.

Professor Greg Jones, University of Otago

The Metformin Aneurysm Trial
48 months, $1,325,323.50

About 3 per cent of elderly New Zealanders have an abdominal aortic aneurysm (AAA), with a greater burden amongst Māori. The widespread use of abdominal imaging means that most AAA are identified when they are small, asymptomatic and at low risk of rupture. Currently, there are no medical therapies to slow AAA growth, with regular surveillance being the only management option, until the aneurysm reaches a size which warrants the risk associated with performing a surgical repair. The Metformin Aneurysm Trial will assess whether 1500mg of metformin a day will reduce AAA-related events among 1500 patients with small AAA. This Australasian-led trial represents the largest AAA drug trial ever performed.

Associate Professor Peter Jones, University of Otago

Role of ryanodine receptors in Alzheimer's disease
36 months, $1,189,936.70

Alzheimer's disease affects about 10 per cent of people aged 65 and older, positioning it as a major concern for New Zealand's aging population. Current treatment options are limited due to an incomplete understanding of the molecular changes occurring within nerve cells. Growing evidence shows that inappropriate leak of calcium within nerve cells, through a protein channel is associated with Alzheimer's. This project will focus on this aspect and examine whether drugs known to prevent calcium-leak in the heart also work in neurons, and consequently may represent new treatments for Alzheimer's disease.

Dr Khoon Lim, University of Otago, Christchurch

Smart delivery of growth factors for treating osteonecrosis of the femoral head
24 months, $730,435.20

Avascular necrosis (AVN) also known as osteonecrosis is a condition when there is a severe disruption in blood flow to the bone, leading to bone death. Extreme cases of AVN lead to the collapse of bone and the surrounding joint, as well as severe pain that interferes with joint mobility. In this project, Dr Lim's team aim to deliver bioactive growth factors through a previously engineered stent, that can aid the regeneration of the disrupted blood vessels to not only prevent the progression of AVN, but also to simultaneously repair the damaged bone.

Dr Melissa McLeod, University of Otago, Wellington

Prioritising Māori health and equity: a critical approach to modelling
36 months, $1,199,300.15

Reducing inequities in health for Māori is an objective of the New Zealand health system. Modelling is a useful tool for estimating the health benefits of interventions to inform decision-making. However, modelling methods take little account of health equity, and are almost always focussed on a single health intervention. In this Māori-led research, Dr McLeod's team will address these limitations by critically examining modelling methods and redesigning them to primarily take account of health equity for Māori. They will focus on cancer screening interventions as an area of high priority for Māori health and inequities. They will build a new model structure that allows combinations of cancer screening interventions to be modelled together and directly compared.

Dr Matthew McNeil, University of Otago

Combating antimicrobial resistance with high throughput bacterial genetics
36 months, $1,199,272.35

Antimicrobial resistance is a major international public health crisis. Central to this problem are drug-resistant strains of Mycobacterium tuberculosis, that have long treatment times and low cure rates. Dr McNeil and his team will develop a novel high-throughput functional genetic platform to identify unique vulnerabilities in drug resistant strains to drive the development of novel drugs and drug combinations. This will be achieved with a level of accuracy and throughput unmatched by classical drug screening.

Professor Lynette Sadleir, University of Otago, Wellington

Genetic Discoveries for Unsolved Developmental and Epileptic Encephalopathies
36 months, $1,199,869.65

The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies affecting 1 in 2000 live births. These disorders, which present in childhood, are catastrophic. One in four children die by 20 years of age and survivors have significant lifelong intellectual, psychiatric, behavioural and motor disabilities. In most children a genetic change causes this severe epilepsy. Although some of these genes have been identified, more than 50 per cent of children still cannot be genetically diagnosed. In this project, Professor Sadleir's team will comprehensively and systematically search the DNA of children with unsolved developmental and epileptic encephalopathies to discover new epilepsy genes. This work will lead directly to improved diagnosis, therapy and outcomes for children with these devastating disorders.

Associate Professor Ivan Sammut, University of Otago

A Novel Therapeutic to Protect Hearts in Acute Ischaemic Procedures
36 months, $1,143,638.85

Heart surgeries involving bypass to correct coronary and valvular disease are commonly performed procedures. Whilst for the majority, the outcome is favourable, the inevitable temporary interruption of blood flow can result in ischaemic damage to the heart evoking severe multi-organ injury. There is a clear need to protect patients against this peri-operative injury. In this project, Associate Professor Sammut's team will trial novel pharmacological agents developed in collaboration with Professor David Larsen to protect cardiac function during bypass procedures. Ultimately, these compounds will be developed as surgical adjuncts to protect the heart and improve patient outcomes.

Dr Caroline Shaw, University of Otago, Wellington

Seeking the transport sweet spot: health, equity and zero carbon
36 months, $1,199,695.10

This project will work with advisors from the New Zealand land transport sector to develop a range of NZ-specific scenarios to reduce land transport emissions and extend an existing model to allow the team to examine the costs, health impacts and greenhouse gas emission changes over time for each different scenario compared to a baseline. The model will report results by age, sex, city, and for Māori and non-Māori, giving the ability to examine potential inequities and consider specific scenarios that might work best for Māori.

Professor Paul Smith, University of Otago

Galvanic Vestibular Stimulation as a treatment for neurological disorders
36 months, $1,188,357.10

Galvanic vestibular stimulation (GVS) is a method of non-invasive electrical stimulation of the balance system in the inner ear (the peripheral vestibular system) that is used to test vestibular reflexes. A variant of this, known as 'noisy GVS' (nGVS), has been reported to be useful in the treatment of various neurological and psychiatric diseases. However, how nGVS acts on the brain is unknown. The aim of this project by Professor Smith and Associate Professor Yiwen Zheng, is to investigate the effects of nGVS in animals and identify the underlying mechanisms. Since recent studies have suggested that nGVS may be useful in the treatment of Parkinson's disease, this project will focus on its effects on a part of the brain that malfunctions in this disease. The results of the study will provide a clearer understanding of how nGVS could be harnessed for the treatment of Parkinson's and other neurological disorders.

Dr Jesse Kokaua, University of Otago

Lighted Paths and Connecting Pathways: Education, Health and Pacific families
36 months, $1,199,999.55

This project leverages off earlier work investigating associations between years of parental education and their children's health. This proposed piece of work will seek to use the longitudinal nature of the Pacific Island Families Study (PIFS) to investigate further the associations between education on the health burden of Pacific families and understand the drivers behind their different progressions. For example, how did Pacific families with generally good health outcomes today, look 10 years ago? In particular, what contributed to families, considered to have fewer opportunities, to continue to comparatively successful health outcomes over time, and did education play a part in that progression?