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Deputy Vice-Chancellor (Research and Enterprise) Professor Richard Blaikie

University of Otago researchers have been awarded more than $24M in new health research funding to support their world-class studies aimed at improving New Zealanders’ health and well-being.

In the Health Research Council (HRC) of New Zealand’s latest annual funding round results announced today Otago researchers gained 19 contracts, including a major multi-million, five-year programme and 18 projects, covering a wide range of health research areas.

The recipients span the University’s campuses in Dunedin, Christchurch and Wellington.

Deputy Vice-Chancellor (Research and Enterprise) Professor Richard Blaikie says the HRC funding serves to illustrate the great breadth, depth and outstanding quality of health research by University of Otago researchers.

"This funding will allow Otago researchers to build upon what they have already done and continue to contribute to improvements in the health and well-being of New Zealanders. Ongoing support from the HRC is central to this, with these prestigious awards recognising the reputation for excellence Otago researchers have forged," he says.

New programme focuses on gastric cancer burden

Professor Parry Guilford in the Department of Biochemistry will lead a five-year programme which has been awarded just under $5M in new funding from the HRC to examine ways of reducing the burden of gastric (stomach) cancer in New Zealand. It is the second greatest cause of cancer death worldwide and in New Zealand its incidence in Māori and Pacific people is three times higher than in non-Māori.

Professor Guilford's programme will include a series of linked, multidisciplinary projects which seek to improve understanding of environmental and genetic risk factors, identify better diagnostic methods, more accurately targeted treatments and improvements in health delivery mechanisms. Gains in these areas would benefit New Zealand's highest risk populations and thereby reduce health inequalities.

18 new Otago projects to tackle a wide range of health issues affecting New Zealanders

Projects covering a variety of health research have also been supported in the latest HRC funding round. They range from and implantable light stimulator to treat Parkinson's disease, to examining community exercise for long-term management of diabetes and multi-morbidity. The grants vary between $485,000 to more than $1.4M, with 13 of the 18 contracts worth more than $1M.

Professor Allan Herbison has been awarded funding for two projects totalling more than $2.25M to extend his fertility research. Both projects will focus on learning more about the gonadotropin-releasing hormone (GnRH) neurons in the brain which are known to control fertility. These projects will provide a foundation for developing new therapies for fertility control in humans.

Several projects involve genetic studies, including a project to identify genes involved in antibiotic resistance in superbugs, other examining genetic variants in brain development disorders, as well as research into genetic changes which can alter the risk of familial breast and ovarian cancer. There will also be a research project into identifying new genetic markers for coronary artery disease.

Other heart related projects include research into reducing the current high heart failure readmission rates, which are considered a global problem. Another study will examine whether current treatments for chronic obstructive pulmonary disease (COPD) are increasing the risk of acute coronary syndrome.

Funding has also been provided for research projects into non-Hodgkin lymphoma (NHL), inflammatory signalling in a range of diseases, and the infection of human cells by Listeria. Other projects include improving access to cervical cancer screening for Māori women, the assessment of frailty in older people, geographic and ethnic inequalities in stroke outcomes, and a study into the impact of racism on the future health of adults.

A $577,528 HRC Pacific project grant has also been awarded to Dr Rosalind Richards to examine sleep and well-being among Pacific children and adolescents.

For more information, contact:

Professor Richard Blaikie
Deputy Vice-Chancellor (Research & Enterprise)
University of Otago
Tel 64 3 479 8513

2017 HRC programme grants - Otago

Professor Parry Guilford, University of Otago, Dunedin
Reducing the burden of gastric cancer in New Zealand
60 months

Gastric (stomach) cancer is the 2nd greatest cause of cancer death worldwide. In New Zealand, it is remarkable for its incidence in Maori and Pacific people being three-fold greater than in non-Maori. It is clear that a significant proportion of the gastric cancer burden in New Zealand could be avoided by an improved understanding of environmental and genetic risk factors, better diagnostic methods, more accurately targeted treatments and improvements in health delivery mechanisms. These gains will have particularly benefit for our highest risk populations, thereby reducing health inequalities. In this research, our goal is to reduce the burden of gastric cancer in vulnerable New Zealand populations through a series of linked, multidisciplinary projects.

Other Otago Named Investigators:
Associate Professor Michael Black
Associate Professor Joel Tyndall
Dr Sharon Pattison

2017 HRC project grants - Otago

Associate Professor Brian Cox, University of Otago, Dunedin
The molecular pathological epidemiology of NHL
18 months

The research will assess the relationship among similar and disparate risk factors for various types of non-Hodgkin lymphoma (NHL) and variations in the gene controlling mechanisms that are passed on when cells divide. The NHL patient series will also provide a basis for survival studies for patients with different types of NHL and allow the impact of new types of therapy to be estimated.

Other Otago Named Investigators:
Professor Ian Morison
Dr Mary Sneyd

Professor Catherine Day, University of Otago, Dunedin
Integration of inflammatory signalling by TNF receptor associated factors
36 months

Initiation and resolution of inflammation is essential for cellular homeostasis, and aberrations are associated with a range of diseases. Regulation of inflammation relies on signals transmitted from receptors on the surface of cells to the nucleus. Often, several cell surface receptors act in combination to elicit a particular inflammatory response. TNF receptor associated factors (TRAFs) are a key family of proteins that recognise many different activated receptors, and translate their signals into an appropriate response. Improper TRAF signalling is implicated in cancer, chronic inflammatory disorders and immune deficiency. The proposed project will investigate precisely how TRAF proteins function in combination with each other to reliably integrate inflammatory signals. This work will provide fundamental knowledge about the mechanisms of inflammatory signalling, identify possible molecular targets for cancer and chronic inflammation, and explain how existing therapies that target immune receptors control downstream signalling pathways might be used for maximum benefit.

Other Otago Named Investigators:
Dr Peter Mace

Professor Leigh Hale, University of Otago, Dunedin
Community exercise for long-term management of diabetes and multimorbidity
36 months

We know that exercise assists the management of diabetes but presently no specific advice is available as to how people can safely and confidently engage in exercise. The Community Exercise Programme (CEP) is an inter-professional coordinated, patient centred, whānau-supported package of care for people living with type II diabetes. It was developed in Dunedin to specifically target Māori and Pacific people and those living in low socioeconomic areas. It combines twice weekly education with tailored exercise for 12 weeks, followed by an ongoing weekly maintenance exercise class. The aim of this exploratory randomised controlled trial is to investigate whether those taking part in CEP have more control of their diabetes and have better health outcomes one year later than people who do not participate in it. We will also find out whether CEP is cost effective and what is required to roll it out into other areas of New Zealand.

Other Otago Named Investigators:
Professor Jim Mann
Professor Timothy Stokes
Dr Ramakrishnan Mani
Dr Prasath Jayakaran
Dr Fiona Doolan-Noble
Dr Trudy Sullivan
Mr Christopher Higgs
Mr Andrew Gray

Professor Allan Herbison, University of Otago, Dunedin
GnRH neuron control of ovulation
36 months

Nearly 40 per cent of women suffering from infertility are unable to ovulate normally. While it is known that the gonadotropin-releasing hormone (GnRH) neurons in the brain control fertility, the molecular and cellular characteristics of the sub-population of GnRH neurons that drive ovulation are not established. This project aims to identify and characterise the specific GnRH neurons responsible for generating the "GnRH surge" that initiates ovulation. This will be achieved by implementing cutting-edge optogenetic neuroscience methodologies. In addition, the use of a novel genetic cell activity detection strategy will allow the electrical membrane properties and gene expression profiles of GnRH surge neurons to be identified. These studies will generate an in-depth understanding of the key cells that drive ovulation and thereby provide a platform for developing therapeutic agents for fertility control.

Other Otago Named Investigators:
Dr Xinhuai Liu
Professor Brian Hyland
Dr Robert Day
Professor Parry Guilford

Professor Allan Herbison, University of Otago, Dunedin
Deciphering the dendron for fertility control
36 months

The gonadotropin-releasing hormone (GnRH) neurons control fertility in all mammals including humans. We have recently discovered that GnRH neurons have a cellular process previously unknown in the central nervous system termed a "dendron". We propose that the unique features of the GnRH neuron dendron allow neural inputs to generate and modulate the pulsatile release of reproductive hormone levels in the blood. Correct levels of hormone pulsatility are critical for fertility. This project will use innovative neuroscience technologies to identify the neural inputs acting upon the dendron and then establish their physiological role in regulating the secretion of GnRH.Together, these studies will determine how this unique neuronal structure operates and provide a foundation for exploring the utility of dendron-targeted therapies for fertility control in humans.

Other Otago Named Investigators:
Dr Michel Herde
Mr Robert Porteous

Associate Professor Keith Ireton, University of Otago, Dunedin
Role of host exocytosis in infection of human cells by Listeria monocytogenes
36 months

Listeria monocytogenes is a potentially deadly cause of food-borne illnesses including meningitis and abortion. Listeria is internalised into human cells and spreads from infected cells to neighbouring healthy cells by generating 'protrusions' - bacteria encased in finger-like projections of the host plasma membrane. How protrusions form and elongate to allow cell-to-cell spread is poorly understood. This proposal tests the novel hypothesis that Listeria subverts the function of a human complex called the exocyst to direct the insertion of host-derived membrane that fuels the growth of protrusions.

Other Otago Named Investigators:
Dr Mihnea Bostina

Dr Hamish Jamieson, University of Otago, Christchurch
Using the InterRAI to improve identification and management of frailty
36 months

Older people with frailty are more vulnerable to sudden declines in health in response to seemingly small trigger events such as drug side effects or overmedication. Identifying older people in the community with frailty offers an opportunity to prevent or delay these adverse events. This study takes advantage of New Zealand’s world-leading comprehensive assessment system for older people (the interRAI). In partnership with Canterbury DHB we will develop and trial a measure of frailty within the interRAI to guide better medication treatment plans and enhance clinical management. We will compare possible measures statistically using existing data and then evaluate the impact of utilising the interRAI to identify frailty and target medication reviews in a stratified randomised-controlled trial. The research may offer a specific workable improvement to the national interRAI assessment system to help prevent unnecessary medication complications and hospitalisations for older people with frailty.

Other Otago Named Investigators:
Dr Prasad Nishtala
Professor Dee Mangin

Associate Professor Greg Jones, University of Otago, Dunedin
An epigenome-wide study for coronary artery disease
36 months

Coronary artery disease (CAD) is the leading cause of death in our community. Unfortunately, current risk prediction tools lack both sensitivity and specificity and there is a clear need to develop improved methods of identifying those at risk. While both inherited and environmental factors each contribute significant risk, our current lack of understanding of gene-environment interactions has limited our ability to identify new adjunctive risk tools. In this study we will use epigenetics, specifically genome-wide DNA methylation profiling, as a marker of some of these interactions, in order to identify novel CAD risk markers. Our own preliminary data, suggests that this approach may not only yield significant advances in CAD risk prediction, but may also identify novel therapeutic targets amenable to drug treatments. By combining genetic, epigenetic and demographic risk information for each study participant this research represents an important step towards the delivery of personalised cardiovascular disease medicine.

Other Otago Named Investigators:
Professor Michael Williams

Professor Iain Lamont, University of Otago, Dunedin
Unmasking genes for antibiotic resistance in a superbug
36 months

The rapid rise of superbugs, bacteria that are resistant to all available antibiotics, is an increasing threat to health with the potential to overwhelm the healthcare system. However, our understanding of how bacteria resist antibiotics is far from complete. During infection the superbug Pseudomonas aeruginosa undergoes multiple mutations and evolves very high antibiotic resistance but only a subset of the mutations causing resistance have been identified. In this research we will obtain the first full overview of mutational events that result in high-level resistance. We will do so by developing highly resistant mutants of P. aeruginosa under controlled laboratory conditions, comparing the underlying mutations with those that occur during infection, and determining the effects of key mutations in a mouse model of infection. The results will provide a major step forward in understanding how bacteria resist antibiotics and may lead to improved treatment regimens for P. aeruginosa and other superbugs.

Other Otago Named Investigators:
Dr Wayne Patrick

Associate Professor Beverley Lawton, University of Otago, Wellington
He Tapu Te Whare Tangata
36 months

Māori women are more than twice as likely to be diagnosed with cervical cancer and three times more likely to die of cervical cancer than Pākehā women. The Human Papilloma Virus (HPV) is the cause of cervical cancer. HPV testing is new technology which will replace present cervical cytology screening in the future. Prevention and early detection remain the key interventions for addressing Māori needs and reducing inequalities in cervical cancer in New Zealand. To meet this need we have designed a community based Kaupapa Māori research project called He Tapu Te Whare Tangata to improve access to cervical cancer screening. He Tapu Te Whare Tangata gives Māori ownership of the process of instigating this innovative HPV screening using a community research partnership model rather than responding to future national models that may not suit Māori needs. To improve health outcomes for Māori its essential to have input and collaboration

Other Otago Named Investigators:
Miss Kendall Stevenson
Dr Dalice Sim
Associate Professor Merilyn Hibma
Associate Professor Peter Sykes
Dr Evelyn MacDonald

Dr Lianne Parkin, University of Otago, Dunedin
Are treatments for COPD increasing the risk of acute coronary syndrome?
36 months

Acute coronary syndrome (heart attacks and unstable angina) and chronic obstructive pulmonary disease (COPD) are among the commonest reasons for hospital admission and death in New Zealand. Māori, Pacific peoples, and lower income groups are particularly affected. Acute coronary syndrome is common among people with COPD. Inhaled long-acting bronchodilators (long-acting muscarinic antagonists [LAMAs] and long-acting beta-agonists [LABAs]) are the main drugs used to treat people with COPD. However, there is concern that both LAMAs and LABAs may further increase the risk of acute coronary syndrome. This is important because the clinical benefits of these drugs are modest and people with COPD are more likely to die from coronary events than from respiratory failure. We propose to undertake a study to determine the risk of acute coronary events in people taking LAMAs and LABAs. The study will use anonymised existing data only, no patients will be approached.

Other Otago Named Investigators:
Dr Jack Dummer
Associate Professor Katrina Sharples
Dr Jiaxu Zeng
Dr Simon Horsburgh
Mr David Barson

Dr Louise Parr-Brownlie, University of Otago, Dunedin
Implantable light stimulator to treat Parkinson’s disease
36 months

Parkinson’s disease (PD) affects 10,000 people in New Zealand. Current drug and deep brain stimulation treatments help reduce symptoms, but they also produce unwanted side effects. We aim to improve the quality of life for PD patients by developing the next generation of deep brain stimulation technology that has greater target specificity and reduced stimulation side effects. We have recently discovered that light stimulation in the brain improves parkinsonian movements. In this preclinical study, we will optimise the effect of chronic light stimulation to improve precise movements and activities of daily living. To do this, we will create an implantable light stimulator capable of delivering high-resolution optical stimulation patterns to support lifetime treatment options for PD patients. Although the project is focused on PD, the light stimulator has broad utility for treating other neurological and psychiatric diseases.

Other Otago Named Investigators:
Professor Dirk de Ridder
Dr Sonja Seeger-Armbruster

Dr Annemarei Ranta, University of Otago, Wellington
Geographic and ethnic inequities in stroke outcomes
36 months

Stroke is the third most common cause of death and the most significant cause of adult disability in New Zealand. We know of several key interventions that reduce disability after stroke. While much effort has gone into implementing these treatments through NZ hospitals it is unclear whether all hospitals achieve the same patient outcomes given existent variation in service set-up. Also, while we know that stroke occurs at a younger age in some ethnic groups (notably Māori and Pacific people) we do not know whether, once the stroke has occurred, they also face poorer access to optimal services. This project aims to investigate potential geographic and ethnic variation in service provision and stroke outcomes to inform the national stroke programme in its efforts to optimise stroke care delivery to all New Zealanders regardless of domicile or ethnic background.

Professor Stephen Robertson, University of Otago, Dunedin
Defining human specific genetic variants in brain developmental disorders
36 months

Stem cells within the developing human brain have the potential to repair neurological damage whether it is caused by in-born or acquired factors. A limited understanding of the genetic regulation of these cells limits the exploitation of this capability. We will study the genetic factors that underpin a disorder caused by mutations that affect brain stem cells. By identifying these factors, particularly those that occur in regions of the genome that are specific to humans, we aim to catalogue factors that will form a lens through which we can understand human brain development better. Aligned with this aim is our intention to study these mutations and their affects in human brain organoids, tiny self-organising brain-like structures that can be grown the laboratory from human cells. Together these experiments will help develop more specific therapies for brain damage that are aimed directly at brain stem cell functions.

Other Otago Named Investigators:
Dr Wenhua Wei

Dr James Stanley, University of Otago, Wellington
The impact of racism on the future health of adults: a prospective cohort study
36 months

Racism – at an individual or structural level – is recognised as an important determinant of health. Most evidence comes from cross-sectional studies, where experience of racism and health status is measured simultaneously, making it difficult to tell whether racism actually causes poorer health. We propose a study to strengthen this evidence base by examining the impact of experience of racial discrimination on subsequent health. We will recruit people who participated in the 2016/17 NZ Health Survey and reported experiencing racism, matching them with other participants (similar by ethnicity, age, socioeconomic status but without experience of racism), and re-interviewing them about their health status approximately two years after their NZHS interview. We can then determine if people who experienced racism had a different change in health in this period. This will strengthen evidence to support developing interventions to reduce levels of racism, reduce inequities and improve New Zealanders health.

Other Otago Named Investigators:
Dr Ricci Harris
Dr Donna Cormack
Professor Richard Edwards
Mr Andrew Waa

Professor Richard Troughton, University of Otago, Christchurch
Reducing heart failure readmission: The IMPERATIVE-HF study
36 months

Heart failure is a common condition and a major cause for hospitalisation in adults. One in four patients hospitalised with HF will be readmitted within 30 days of discharge. These very high readmission rates are a global problem for which no effective strategy has yet been found. The IMPERATIVE-HF study is testing a new strategy to reduce heart failure readmission. We are using blood levels of the heart hormone NT-proBNP to guide the management of heart failure from the time of hospital discharge and testing whether this reduces readmission and improves survival in the first 3 months after discharge compared to usual care guided by clinical assessment alone. If successful, the study findings can be immediately applied to clinical care and incorporated into international guidelines for heart failure management

Other Otago Named Investigators:
Professor Christopher Frampton
Professor Mark Richards

Dr Logan Walker, University of Otago, Christchurch
Genetic modifiers of risk of familial breast and ovarian cancer
36 months

The recent development of new gene screening technologies has revolutionised genetic testing of high-risk breast and ovarian cancer patients. Genetic information from these technologies is vital for directing clinical care of patients and their families and has significant implications for disease prevention. Approximately 1/250 individuals inherit a genetic mutation in the genes BRCA1 or BRCA2, which means they are at high-risk of developing breast and ovarian cancer. However, the risk of cancer for these individuals varies significantly due to other (unknown) genetic changes, creating a significant challenge for counselling and clinical decision making. Our proposal aims to exploit a large international collaboration to identify and functionally characterise genetic changes which modify the risk of breast and ovarian cancer in women who have inherited a BRCA1/BRCA2 mutation. Discoveries from this unique proposal will facilitate accurate clinical decision making, and provide new insights into the aetiology of breast and ovarian tumour development.

Other Otago Named Investigators:
Dr Peter Mace
Dr John Pearson

2017 HRC Pacific project grants - Otago

Dr Rosalina Richards, University of Otago, Dunedin
Sleep and well-being among Pacific children and adolescents
32 months

Ensuring children and adolescents receive sufficient good-quality sleep is critical for their physical and emotional health. We currently know little about sleep in Pacific children and their families and how to best support good sleep/wake patterns within Pacific contexts. The overarching objective of this project is to inform the development of effective sleep interventions by capturing Pacific perspectives about sleep, health and interventions. The first study will involve interviews with Pacific parents, exploring intergenerational changes in sleep patterns, associations between sleep and wellbeing and appropriateness of current sleep measurement and intervention strategies. A second study will use key informant interviews with Pacific health and educational professionals to explore the role of sleep in health/education outcomes for Pacific families and explore ways to maximise the effectiveness of sleep interventions for Pacific communities.

Other Otago Named Investigators:
Associate Professor Barbara Galland
Associate Professor Ruth Fitzgerald
Professor Rachael Taylor

A list of Otago experts available for media comment is available elsewhere on this website.

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