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Otago researchers have received a significant $52 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. Additionally, a 12-month, $1 million extension for an existing Dunedin Study Programme Grant was 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). 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 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? Professor Richie Poulton, University of Otago A lifecourse study on ageing processes to inform early intervention strategies 12-months, $1,000,000 programme extension As the population ages and life expectancy increases, policy-makers and citizens are concerned that our extra years should be healthy, productive, and enjoyable, not extra years of disease and disability. Finding new strategies to prevent age-related disease and disability requires identification of risk factors in early-to-midlife that can be ameliorated or reversed, well before the onset of age-related disease. This recognition lends new scientific significance to studies that have followed cohorts from childhood to midlife, including the Dunedin Study. The proposed work will use biomarker data collected from the same 1000 individuals at ages 26, 32, 38, and 45 to track the pace of their biological aging. We will uncover why some people age faster than others, and why some fortunate people age more slowly than their age-peers. Findings are expected to support interventions to slow aging, prevent age-related diseases, and enhance preparedness for wellbeing in later life. Professor Leigh Hale, 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, 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. 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, University of Otago 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, University of Otago 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. Caroline Halley, University of Otago, Wellington 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, University of Otago 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, University of Otago 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, University of Otago 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