From left, Associate Professor Jason Gurney, Professor Rachael Taylor and Professor Richie Poulton.
Otago researchers have received a significant $51 million funding boost from the Health Research Council of New Zealand.
The Programme Grant funding, announced today, alongside Project Grant funding announced last week, will support 31 research projects that will benefit the health and wellbeing of New Zealanders.
Four Programme grants worth $5 million each over five years, a Rangahau Hauora Māori Health Project, a Pacific Health Project, and 24 Project Grants, each running over three years, were all awarded.
HRC Chief Executive Professor Sunny Collings says the research supported by Programme funding should make a significant difference to health and help advance its field of research, while the Project Grants provide exciting opportunities to help advance our knowledge and drive meaningful change in the health system.
Deputy Vice-Chancellor, Research and Enterprise, Professor Richard Blaikie is thrilled with the funding received.
“This is the largest amount of Health Research Council funding Otago has been awarded in any year, which is great news to be able to share with our University community, and the wider public, at this time.
“The funding is recognition of Otago's world-leading researchers, and the needs of the communities they serve.
“We are grateful the Health Research Council has again been able to support their work, which we know will have an enduring impact on the lives and wellbeing of so many.”
The HRC awarded $88.7 million in the past week, including seven Programme Grants ($35 million in total), two Rangahau Hauora Māori Project Grants ($2.4 million in total), three Pacific Project Grants ($3.4 million in total) and 39 General Project Grants ($47.9 million in total).
Professor Leigh Hale and Professor Antony Braithwaite.
HRC 2023 Project and Programme grant recipients
Programme recipients:
Associate Professor Jason Gurney (Ngāpuhi, Ngāti Hine), University of Otago, Wellington
Whakatōmuri, whakamua: Walking backwards into the future of Māori cancer care
$4,999,905
Māori have poorer cancer survival for 23 of the 24 most common cancers diagnosed in New Zealand. There is evidence that Māori are less likely to receive best-practice care during their cancer journey, and this may contribute to these unacceptable differences. In this programme, we will use a mixture of quantitative and qualitative methods to explore aspects of the availability, affordability and acceptability of cancer care for Māori and their whānau, with a view to informing improvements in care access and survival outcomes.
Professor Leigh Hale and Mrs Bernadette Jones, University of Otago
Taunakitanga Takitini: reframing self-management support for all in Aotearoa
$4,999,810
The Taunakitanga Takitini programme aims to build Aotearoa-specific knowledge about supported self-management to enable those who experience greatest health inequities, that is, underserved populations living with lifelong conditions (specifically Māori and Pacific peoples, Tāngata Whaikaha (Māori with disability) and those experiencing learning (intellectual) disability) and their whānau to be supported to live the best possible life. Partnering with Māori, Pacific and disability healthcare providers we will explore service users and communities needs and aspirations for living well and what healthcare services would best support them and how. Using this knowledge, we will co-develop care models of how collaborative community healthcare professionals and kaiāwhina can support and work alongside whānau and communities to enable them to support themselves within their own context. These models will then be implemented, and outcomes evaluated. Our findings will inform policy, healthcare service and the public. We will thereby build Aotearoa-specific research capacity and capability.
Professor Antony Braithwaite and Associate Professor Tania Slatter, University of Otago
Investigating the functions of p53 isoforms and their clinical translation
$4,999,701
This programme focusses on understanding how the TP53 gene network, especially p53 isoforms, contributes to cancer, and using this information to develop clinically useful information and tools. We will verify that high levels ∆133T53b isoform predict which patients will develop aggressive disease and develop a clinically useful biomarker; learn more about the cancers with high levels ∆133T53b by characterising the immune cell infiltration; use CRISPR to identify mechanisms of isoform function; develop novel strategies to target cancers with elevated levels of ∆133p53 isoforms, including immunotherapy; and develop more refined future biomarkers using advanced statistical tools to compare each tumour's immune status and clinical features of cancer patients. With these broad approaches we will develop an in-depth understanding of how the TP53 network contributes to cancer which will provide clinically translatable information leading to new prognostic markers and new therapies.
Professor Rachael Taylor, University of Otago
Whakatipu rakatira: improving sleep as a vehicle to grow healthy future leaders
$4,999,677
We all know the value of a good night's sleep. Yet, for many reasons, good sleep health is often not prioritised, meaning many children and adolescents do not get enough good-quality sleep that lets them function well in today's busy world. Our programme aims to change that – to test different ways of helping tamariki in Aotearoa sleep well, from infancy through to adolescence. Projects include working in conjunction with Māori health providers to develop more comprehensive service delivery around sleep in babies, testing the appeal and effectiveness of different online approaches to improving sleep in younger teens that can be quickly scaled, and school-wide initiatives that allow all older teens to benefit from later school starts that more closely match their biological tendency to sleep late. By working closely with health and education providers, rapid implementation is both feasible and attractive; after all, who doesn't like a good moe?
Project recipients:
Dr Charlene Rapsey, University of Otago
Connected: Who benefits from online delivery of mental disorder treatment?
$1,439,846
Early treatment of mental disorders is essential to reduce suffering and to decrease early mortality. Most prevalent among rangatahi aged 16-24, untreated mental disorder affects relationships, education, and career options. The need for treatment far exceeds resources, with rangatahi Māori less likely to be engaged in treatment. Culturally responsive, online therapies are a cost-effective scalable option to meet the high level of need. Using a pragmatic RCT we will test three internet-therapies (iStandard, iCoach, iGroup), which vary according to external support and strengthening of whakawhanaungatanga. We will recruit rangatahi enrolled in tertiary education. Beyond evaluating which therapy works best overall for Māori and non-Māori, we will use machine learning techniques to understand who is most likely to respond to which treatment. Precision treatment enables an individual to be directed to a treatment with the greatest likelihood of success for them, reducing treatment failure and reducing time to remission.
Associate Professor Peter Jones, University of Otago
Establishment of a new molecular target for arrhythmias and heart failure
$1,198,100
A heart attack, otherwise known as a myocardial infarction, is the second leading cause of death in New Zealand. Those who survive suffer from arrhythmias and heart failure. Unfortunately, there are limited treatment options available for these patients. Diabetes exacerbates these outcomes with diabetic patients experiencing greater mortality and morbidity following a myocardial infarction. Arrhythmias and heart failure are both caused by 'calcium leak' through a protein known as the cardiac ryanodine receptor (RyR2). We have recently found that calcium leak increases when RyR2 phosphorylation by casein kinase 2 (CK2) decreases. CK2 activity is reduced during and after a myocardial infarction, and in diabetes and heart failure. Therefore, this project aims to determine if maintaining the phosphorylation of RyR2 by CK2 can prevent calcium leak, arrhythmias and heart failure in diabetes and following a myocardial infarction. In doing so it will identify a new target for treating arrhythmias and heart failure.
Professor Greg Anderson and Dr Caroline Decourt, University of Otago (co-leaders)
Curbing the reproductive hormonal axis to control PCOS
$1,199,989
Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Although some treatments for symptoms exist, there is currently no cure and infertility remains an intractable problem for many PCOS sufferers. We propose to develop clinically translatable protocols for ovulation induction in infertile women with PCOS. Our approach will be to temporarily suppress pulsatile secretion of luteinising hormone, which is in excess in women with PCOS and causes reproductive dysfunction, in order to reset ovarian follicle development. We will achieve this by targeting kisspeptin or AgRP neuronal systems, which are known to modulate luteinising hormone pulses. Our experiments will utilise transgenic technologies and a preclinical rodent model of hyperandogenic PCOS. We will also test pharmacological compounds which are currently under development as therapeutic drugs, so our results should directly inform clinical translation. We will also evaluate long-term effects of these interventions on a wide range of PCOS symptoms.
Professor Merilyn Hibma, Associate Professor Peter Sykes and Gregory Gimenez, University of Otago (co-leaders)
A molecular triage test to reduce colposcopy referrals after HPV testing
$1,199,987
In 2023, the primary test for cervical screening will change to human papillomavirus (HPV) testing. HPV testing can be carried out on a self-collected swab, improving accessibility of screening for Māori and other women. However, a follow-up invasive triage test may be required. Additionally, many women referred to colposcopy following an HPV+ test do not have disease and would be better managed with monitoring. The purpose of this research is to develop a triage test for HPV+ women using the cells from a self-collected vaginal swab that will distinguish high-grade disease requiring treatment from low-grade disease that can be monitored. RNA sequencing will be used to identify disease-associated changes in gene expression and an assay will be developed and evaluated for its diagnostic effectiveness in a cross-section of HPV+ women. If successful, this test will have a significant impact on women's health and on health delivery nationally and globally.
Dr Caroline Halley and Professor Julian Crane, University of Otago, Wellington (co-leaders)
Urban farm-like dust: microbial origin and protective effects on later asthma
$1,196,994
New Zealand has high rates of asthma and hospitalisations for asthma. A follow up is proposed for a study carried out in 450 urban Wellington homes, to examine whether the recently discovered protection for wheeze by 'farm-like' microbes found in the initial study, have resulted in less asthma at age 12, than those who did not have 'farm-like' dust. Additionally, refining the Finnish 'farm-like' dust and investigating what factors create farm like dust in urban environments is proposed. Understanding these factors gives us our first opportunity to confer the protective effects of farming to urban settings, by modification of the early infant indoor environment.
Professor Suetonia Palmer, University of Otago, Christchurch
IMPEDE-PKD: Metformin to protect kidney function in polycystic kidney disease
$1,440,000
IMPEDE-PKD is a clinical trial evaluating whether metformin prevents kidney failure in people with polycystic kidney disease (PKD). PKD is a genetic condition causing large kidney cysts. Affected people often require dialysis or a kidney transplant and can experience pain and disfigurement. There is no targeted treatment to prevent cyst growth for patients in Aotearoa/New Zealand. The IMPEDE-PKD trial will involve 100 patients in New Zealand with PKD and decreased kidney function. Patients will receive either metformin or a matching placebo for two years. We will evaluate whether metformin slows kidney failure after two years of treatment. Whanau Māori will be partnered with a navigator Māori to provide culturally specific support while participating in IMPEDE-PKD.
Dr Sunali Mehta, University of Otago
Relaxed quality control: how rogue AS-NMD drives cancer evolution
$1,185,000
Cancer cells are continuously evolving under selective pressure by increasing their protein repertoire. This feature of cancer cells is driven by their ability to generate new RNA species via alternative splicing (AS) in combination with relaxing the quality control mechanism called nonsense-mediated mRNA decay (NMD). However, how cancer cells manipulate AS and NMD remains poorly understood. Our study will use cutting-edge gene editing CRISPR-Cas9 technology coupled with long read RNA-sequencing to gain critical insight into how cancer cells exploit AS and NMD to express aberrantly spliced transcripts capable of driving cancer evolution, metastasis and treatment resistance.
Dr Ben Beaglehole, University of Otago, Christchurch
Ketamine versus Ketamine plus Behavioural Activation Therapy for Depression
$1,194,435
Major Depressive Disorder (MDD) is the most common psychiatric disorder. Usual treatments for MDD have limitations including side effects and inadequate response rates. Consequently, Treatment-Resistant MDD (TR-MDD) causes significant individual suffering and high societal burdens. Ketamine offers new opportunities as a highly effective short-term treatment for TR-MDD but relapse rates are high following treatment with Ketamine ending. Treatment guidelines recommend complementing medication treatment of MDD with therapy to improve response and delay relapse. However, the vast majority of Ketamine studies evaluate Ketamine treatment alone. It is not known if the addition of therapy to Ketamine treatment prolongs the clinical response and delays relapse for TR-MDD. We therefore propose a pilot study comparing Ketamine with Ketamine plus Behavioural Activation Therapy (BAT) to evaluate whether BAT (an evidence-based therapy for MDD) prolongs the clinical response and delays relapse following a course of Ketamine treatment.
Dr Ashleigh Barrett-Young and Professor Richie Poulton, University of Otago (co-leaders)
Blood-based biomarkers of dementia in a longitudinal birth cohort
$1,200,000
Finding out if you have the early signs of Alzheimer's disease from a simple blood test is getting closer to reality. In this project, we will investigate promising blood biomarkers of dementia, including pTau181, pTau217, amyloid beta (AB40 and AB42), neurofilament light chain, and glial fibrillary acidic protein, in middle-aged members of the Dunedin Study. Participants will be aged 52 so this project will tell us a lot about the processes of Alzheimer's disease and other dementias in their earliest stages, and may help to identify people who are at risk of developing Alzheimer's before they begin to show symptoms, when lifestyle and pharmacological treatments may be most effective. The wealth of data on the Dunedin Study members also gives us an unparalleled opportunity to investigate the risk and protective factors from across the lifecourse which may influence a person's risk of developing Alzheimer's disease.
Dr Carrie Ruth Innes, University of Otago, Christchurch
Where are the inequities in the journey from health to gynae cancer in Aotearoa?
$1,187,766
Compared with non-Māori, Māori and Pasifika wāhine have a higher incidence and mortality from gynaecological cancer in Aotearoa New Zealand. Of particular concern, the incidence of endometrial cancer in young women in Aotearoa is increasing faster than anywhere else in the world and the greatest burden of this lies in Māori and Pasifika wāhine. Inequities can occur at any stage along the pathway from health to gynaecological cancer and also between different ethnicities and geographical regions. This research study will identify the cultural, geographical, and timeline inequities in the journey from health to gynaecological cancer across all of Aotearoa. Through investigation of health data and interviews with wāhine newly-diagnosed with gynaecological cancer, we will document the ethnicity, timetable, and geographical location, of presentations to health care services, clinical investigations, stage and disease burden at diagnosis, and consider barriers to accessing health care or investigations.
Dr Esther Willing and Dr Amber Young, University of Otago (co-leaders)
Protecting hapū māmā and pēpi from vaccine preventable diseases
$1,158,530
Immunisation against pertussis, influenza, and COVID-19 during pregnancy is the only effective way to protect hapu māmā and their pēpi from these potentially fatal diseases. Maternal immunisation coverage is below optimal in Aotearoa and significant inequities exist for wahine Māori, putting Māori māmā and their pēpi at higher risk from vaccine-preventable diseases. Barriers to maternal immunisation include costs to access services, mistrust of the health system and lack of appropriate information. We will identify and develop interventions to overcome these barriers and improve vaccination uptake for hapu māmā within localities that have significant inequities. We will engage with key stakeholders in these localities including immunisation coordinators, midwives, GPs, pharmacists, iwi, community representatives to co-design interventions to address the specific needs of Māori whanau. We will evaluate these interventions and develop a roadmap for action to decrease barriers to maternal vaccination, support informed decision-making, and improve maternal immunisation coverage across Aotearoa.
Dr Euan Rodger and Associate Professor Aniruddha Chatterjee, University of Otago (co-leaders)
Identifying epigenetic markers for early detection of colorectal cancer
$1,199,979
Colorectal cancer (CRC) death rates are particularly high in Aotearoa New Zealand and are increasing in younger people (age <50 years) and Māori, who are more likely to present with advanced stages of disease. Prognosis and survival of CRC patients rely heavily on the stage at diagnosis. Therefore, there is an urgent need for accessible and easily clinically-deployable biomarkers that enable early diagnosis and improve CRC outcome. Recent work demonstrates that DNA methylation patterns could be used as a powerful tool for highly specific and highly sensitive early tumour detection. We aim to use unbiased whole genome-scale analysis to identify DNA methylation markers in the blood that can be used for minimally invasive early detection of CRC patients. In the future, our work will contribute further to enhanced surveillance for relapse and treatment response to improve CRC outcomes in New Zealand.
Professor Philip Hill and Dr Nina Scott, University of Otago (co-leaders)
Towards tuberculosis elimination for Māori
$1,135,327
This project concerns elimination of tuberculosis (TB), which causes a million deaths per year globally. Amongst New Zealand-born TB cases, 49 per cent are Māori, with a rate over five times that of New Zealand Europeans. We will use an integrated co-design strategy guided by kaupapa partners in Waikato; Whānau Hauroa Assessment (WHĀ) to assess and provide holistic wellbeing needs; a refined case contact engagement strategy to identify latent TB infection and TB cases in whānau of known TB cases, followed by expanded engagement through social network construction and analyses; quantitative and qualitative evaluation of the intervention; and development of a template design for roll-out to other regions in New Zealand. This study will build a pathway towards elimination of TB for Māori, creates opportunity for accelerated hauora gain for individuals, their household and wider whānau, and will build human capacity to lead a future elimination strategy.
Dr Rachel Purcell and Professor Francis Fizelle, University of Otago, Christchurch (co-leaders)
Targeting the tumour microenvironment to improve outcomes in rectal cancer
$1,200,000
The incidence of rectal cancer is increasing in NZ, particularly in younger people (< 50 years). Radiotherapy is often used to treat rectal cancer but patients have varying response, and currently, there are no predictive biomarkers of response available. Our recent work has identified an immune signature in rectal tumours that is predictive of response to radiotherapy, and, based on this, we will validate a biomarker test in an international cohort to predict response to radiotherapy and better direct treatment for rectal cancer patients. In addition, we found that the immune signature is linked to a specific tumour microbiome. We will use state-of the art techniques to determine the tumour immune-cell microenvironment that co-operates with radiotherapy and explore the potential of microbiome-based interventions to improve response to radiotherapy. This work will lead to the development of novel tests and microbiome-based treatments for rectal cancer, and ultimately improve outcomes for cancer.
Professor Nicole Roy, University of Otago
Effect of an Aotearoa NZ Diet for metabolic health on the gut microbiome
$1,174,972
Will the consumption of an Aotearoa NZ Diet that includes a preponderance of plant-based foods, together with lean protein (seafood, lean red meat, and dairy), offer health benefits to people at risk of cardiometabolic disease? What is the role of the gut microbiome in these responses? Such plant-based dietary patterns (e.g., Mediterranean diet, MedDiet) can improve metabolic, cardiovascular, and wellbeing profiles in at risk of cardiometabolic disease. The gut microbiome is increasingly recognised to modulate the protective associations between MedDiet and cardiometabolic disease risk; however, these associations are unknown for an Aotearoa NZ Diet. With the high rates of cardiometabolic disease in New Zealand, and our unique population, understanding these associations is fundamental to improving health. This project aims to understand the influence of such a diet on the composition and function of the gut microbiome and associations with metabolic health outcomes and biomarkers of cardiometabolic disease risk.
Professor Sarah Derrett and Professor Emma Wyeth, University of Otago (co-leaders)
Hinapouri ki Hinatore: Improving mental health outcomes and services
$1,199,862
In New Zealand, specialist mental health and addiction service users (SMHAS-users) experience reduced life expectancy and greater morbidity than the general population. Māori SMHAS-users experience disproportionate health inequities. Poor outcomes are frequently attributed to comorbidities or lifestyle, but structural factors, such as 'siloes' between different parts of our health system, are also important. To improve SMHAS-users' outcomes, integrated care has been called for in He Ara Oranga and elsewhere. We have developed and pre-tested two measures of integrated care for SMHAS-users (JUST) and -staff (JUST-Staff). We will use these measures in two larger surveys of Te Whatu Ora–Southern's SMHAS-users and staff to assess their psychometric performance, and understand how they relate to health and wellbeing outcomes, before recommending their wider use throughout New Zealand. Additionally, two qualitative studies (including a Kaupapa Māori Study) will provide rich insights into approaches, mechanisms and processes supporting integrated care.
Associate Professor Allan Gamble, University of Otago
Cancer targeted bioorthogonal prodrugs
$1,199,997
Drugs used to treat cancer need to be targeted to tumours, otherwise the therapy might fail and the patient will experience side effects. Carrying drugs in an inactive form (prodrug) and then releasing the active drug at the tumour site can reduce side-effects, but limitations still exist. We will investigate a new way to activate prodrugs specifically at the tumour using a bioorthogonal chemical reaction. A small chemical reagent will be attached to a tumour-specific targeting ligand that seeks out tumour cells and sticks to them. The pre-targeted reagent will then “catch" the prodrug and “release” the active drug. New Zealand has one of the highest rates of colorectal cancer in the world and there is a high disparity for Māori patients who are 46 per cent more likely to die than non-Māori patients. Therefore, we will exemplify our strategy in a colorectal cancer model, building New Zealand's capacity in cancer-targeted prodrugs.
Professor Gisela Sole, University of Otago
Stepped rehabilitation for people with persistent shoulder pain
$1,187,251
A shift from passive to active self-management of musculoskeletal disorders has been called for, including shoulder pain, one of the most common types of musculoskeletal pain. Long waiting lists and frequent cancellation for specialist orthopaedic care occur in the national health system. A new approach is needed to improve access to shoulder rehabilitation while minimising cost. The primary aim of this randomised clinical trial is to define the effectiveness of a Stepped Care Model for persistent rotator cuff shoulder pain, compared to usual, pragmatic physiotherapy. The second aim is to explore patient perspectives and experiences of the interventions. The third aim is to evaluate the cost-effectiveness of the Stepped Care Model with pragmatic physiotherapy. We hypothesize that a Stepped Care Model will be equivalent to those of pragmatic usual physiotherapy for people with RCRSP for patient-reported outcomes and have lower individual and health system costs than usual.
Dr Htin Lin Aung and Gregory Gimenez, University of Otago (co-leaders)
Understanding inequitable tuberculosis transmission in Aotearoa
$1,180,729
In Aotearoa New Zealand tuberculosis (TB) disproportionally affects Māori and Pasifika particularly children under five and 5-14 years, suggesting ongoing transmission is occurring in these communities. Adding to this problem, there are variants of TB-causing Mycobacterium tuberculosis bacteria which predominate in these communities. Our research project will investigate TB transmission in Māori and Pasifika communities, by combining the expertise of bacterial genetics, epidemiology, and social science research teams. This will involve working alongside communities and combining expertise from public hospitals, New Zealand universities and Te Whatu Ora in a collaborative approach. Utilising this culturally-responsive, transdisciplinary approach, our research project also aims to serve as a blueprint to tackle other infectious diseases in New Zealand and promote better health outcomes for New Zealanders.
Professor Antony Braithwaite and Dr Kunyu Li, University of Otago (co-leaders)
A role for p53 isoform Δ133p53 in the progression of inflammatory bowel disease
$1,199,999
Inflammatory bowel disease (IBD) is a life-long condition that has significant health and economic impact worldwide, including in New Zealand. Our previous studies show that there is a trend toward higher expression of a p53 variant, Δ133p53 in the inflamed bowel of IBD patients who had either dysplasia or colorectal cancer (CRC), compared to patients without progressive disease. Our studies in an animal model of colitis also show that mice overexpressing an analogue of the human Δ133p53 variant, Δ122p53, had elevated levels of inflammation and severe bowel damage. Here, we propose that Δ122p53/Δ133p53 drives an exaggerated immune response to promote the initiation and development of IBD. We will test our hypothesis using our animal colitis model and bowel tissue samples from IBD patients with and without CRC. The findings of this research provide significant knowledge and potential biomarker and/or target for diagnosis and better treatment options for IBD and CRC.
Professor Christopher Charles and Dr Nicola Scott, University of Otago, Christchurch (co-leaders)
PDE9: inhibition in experimental MI and plasma levels in human heart disease
$1,194,867
Heart disease remains a leading cause of death and disability in New Zealand. Myocardial infarction, commonly known as a heart attack, is a key cause of progressive heart disease. A heart attack results in permanent damage to the heart, that can progress to heart failure and eventually death. New and more effective treatments are needed. The present application aims to assess the effectiveness of a new treatment strategy (inhibition of the enzyme PDE9) administered at the time of heart attack. We will assess its ability to improve the long-term changes in heart structure and function that occur following a heart attack. This may prevent or slow the progression to heart failure. We will also measure levels of the PDE9 enzyme in blood from patients with heart disease to determine whether this gives important information on severity of disease or best treatment options.
Professor Julia Horsfield and Dr Jisha Antony, University of Otago (co-leaders)
Fighting leukaemia colonisation of the haematopoietic niche
$1,198,340
Acute myeloid leukaemia (AML) has a low survival rate of 22 per cent in New Zealand. Treatment options for AML are limited and new strategies are needed to combat this disease. Understanding the function of AML-associated gene mutations is required to develop new therapies. Mutations in genes of the cohesin complex are present in ~12-20% of AML. Leukaemia stem cells can survive and evade treatment through interaction with the surrounding microenvironment known as the 'niche'. We found that cohesin mutation enhances adhesive characteristics of leukaemia cells. We propose that these characteristics could promote increased interaction and colonisation of the leukemic cells into the niche. Zebrafish are an excellent model to study leukaemia development in vivo. This project will utilise cohesin mutant zebrafish models to examine the interaction and invasion potential of cohesin mutant cells within the niche, and determine whether niche interactions can be targeted for therapeutics.
Professor Rebecca Campbell, University of Otago
Identifying central therapeutic targets in polycystic ovary syndrome
$1,198,921
Polycystic ovary syndrome (PCOS) is a prevalent and poorly understood disorder, characterised by high circulating levels of 'male-typical' androgen hormones and infertility. There is a desperate need to better understand this personally and economically costly disorder to identify therapeutic targets. We propose to use the latest generation of intersectional transgenic tools in a well-characterised preclinical model of PCOS to hone in on the key androgen targets in the brain that mediate reproductive dysfunction and to determine the causal mechanisms involved. We will also investigate the impact of clinically relevant anti-androgen therapies on the specific brain mechanisms associated with PCOS pathology. This work will provide valuable new knowledge on the forefront of biomedical research aimed at understanding PCOS pathogenesis and treatment and steroid hormone signalling in the female brain.
Professor Kurt Krause, University of Otago
Targeting microbial energetics to achieve a rapid cure for tuberculosis
$1,199,909
Tuberculosis remains a leading cause of death from infectious diseases worldwide and the spread of drug-resistant tuberculosis threatens to return us to the pre-antibiotic era for this disease. However, a game changer in combatting TB has arisen from work showing that a tuberculosis protein called bd oxidase is central to allowing this bacterium to survive during latent infection as well as under antibiotic treatment. Evidence has emerged that inhibiting bd oxidase during anti-tuberculosis therapy could allow for the rapid elimination of TB - over weeks rather than many months, as currently required. We will employ a multi-disciplinary approach comprising molecular microbiology, medicinal chemistry and the recent high-resolution Mycobacterium tuberculosis bd oxidase structure from our research team to identify and speed the development of bd oxidase inhibitors. Our findings may ultimately lead to a new class of anti-tuberculosis compounds and to a rapid cure for this ancient and deadly disease.
Rangahau Hauora Māori Health Project:
Dr Paula Toko King (Te Aupōuri, Te Rarawa, Ngāpuhi, Ngāti Whātua, Waikato Tainui, Ngāti Maniapoto), University of Otago, Wellington
Ngā Hau o Tāwhiri – Returning our Mokopuna to the winds of Tāwhiri
$1,199,965
Similar to the situation for indigenous children and young people worldwide, mokopuna Māori experience unjust incarceration on a mass scale in New Zealand. Improving community re-entry wellbeing is a critical step toward advancing decarceration of mokopuna from youth justice residences and prisons. Developed with our community-based rangatahi Māori research partners, this Kaupapa Māori mixed-methods research is inspired by the whakataukī, “E hoki koe ki ōmaunga kia purea koe e ngā hau o Tāwhirimātea”. 'Ngā Hau o Tāwhiri' is a metaphor for fresh, new mokopuna Māori-led solutions that focus on community re-entry wellbeing. We will use routinely collected government data to understand community re-entry pathways for mokopuna aged 10–19 years, and factors influencing wellbeing outcomes. We will undertake ethical co-designing with mokopuna with lived experience of incarceration, supporting the development of mokopuna to become skilled researchers in the design of strategies for self-determined pathways supporting positive community re-entry wellbeing.
Pacific Health Project:
Professor Daryl Schwenke, University of Otago
Can loss of a 'hunger' hormone increase cardiovascular disease in Pacific people
$1,199,984
In New Zealand, Pacific Island peoples (PI) are disproportionally over-represented in those with diabetes and cardiovascular disease (CVD). The reasons for this disparity remain unclear. The 'hunger' hormone ghrelin is known to protect against CVD, in part, by silencing the 'sympathetic' nerves that stress cardiovascular function. Preliminary clinical data reveals that ghrelin is adversely reduced in people with diabetes. This study aims to show that ghrelin is lower in PI compared to non-PI, which would explain why PI are predisposed to CVD. We will measure ghrelin in blood samples from healthy PI and New Zealand European subjects, as well as people with diabetes, and determine whether reduced ghrelin levels drive a dangerous increase in sympathetic activity, which is known to underpin many cardiovascular morbidities. Finally, ghrelin and sympathetic activity will be compared between New Zealand-Pacific vs indigenous-PI to differentiate between environmental and genetic factors contributing to CVD.