Annual Grants

Aotea Group Holdings Limited and H Robert Wilson (Funders)

Potentially avoidable hospitalisations among autistic young people in Aotearoa New Zealand

Principal investigator: Dr Emma Heydon, Department of Paediatrics and Child Health, University of Otago

Co-investigators: Dr Nick Bowden, Mrs Joanne Dacombe, Professor Barry Taylor, Department of Paediatrics and Child Health, University of Otago

Autistic children and young people often find interactions with healthcare more challenging than others their age. Our previous research has shown that many hospital stays for these young people could be avoided. This study will use nationwide hospital data in New Zealand to explore the specific types of potentially preventable hospitalisations Autistic children and young people are admitted for, and which sub-groups are most affected (e.g. by age, sex, and co-occurring intellectual disability). Understanding who is affected is the first step towards identifying how health services could be improved to reduce preventable hospital admissions, and the stress incurred if admission is needed, for Autistic young people and their families.

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Aotearoa Gaming Trust (Funder)

A novel pathway protecting bone during lactation

Principal investigator: Dr Siew Hoong (Joe) Yip, Department of Anatomy, School of Biomedical Sciences, University of Otago

Co-investigators: Prof David Grattan, Luis Wei Cheng Lim (PhD student), Department of Anatomy, School of Biomedical Sciences, University of Otago

During breastfeeding, mothers lose a lot of calcium to produce milk, which can weaken their bones. A recent study discovered that kisspeptin cells, usually involved in controlling fertility, help protect bone health during this time. These cells start making a protein called CCN3, which helps strengthen bones. We hypothesize that the maternal hormone called prolactin might trigger this change. We will investigate this by using a mouse model that doesn’t have prolactin signals in these kisspeptin cells. This research could help us better understand how the body protects bones during breastfeeding and may lead to new treatments for osteoporosis.

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Estate of Frances Kenney Miles (Funder)

Characterising and identifying ways to target cancers with H179 TP53 mutations

Principal investigator: Dr Sunali Mehta, Department of Pathology, Dunedin School of Medicine, University of Otago

Co-investigators: Dr Debina Sarkar and Dr Aaron Jeffs, Department of Pathology, Dunedin School of Medicine, University of Otago

Cancer is a major global and New Zealand-wide cause of death, with TP53 mutations (a genetic alteration) affecting over 50% of cancers. Patients with TP53 mutations have lower survival rates. However, cancers are not assessed for TP53 mutations during diagnosis and treatment due to the lack of knowledge about their impact on treatment response. This study aims to use innovative tools to determine the effect of an uncharacterised TP53 mutations (H179R/Y) and identify the best treatment strategy for these patients. In the future, outcomes from this study may help doctors effectively treat cancers with H179 TP53 mutations.

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H Robert Wilson (Funder)

Testing a novel therapy for frontotemporal dementia

Principal investigator: Dr Owen Jones, Department of Psychology, University of Otago

Co-investigators: Prof Wickliffe Abraham, Department of Psychology, University of Otago

Frontotemporal dementia is a neurodegenerative condition that has no cure or treatment. Accordingly, we need new therapies targeting the earliest stages of the disease that drive later, catastrophic brain damage. We have new evidence that certain calcium channels in nerve cells are overly active very early in the disease. This could be key, as too much calcium is toxic to cells. Fortunately, several drugs that block calcium channels are already available for treating other conditions. This project will test the ability of one such drug to protect against brain cell loss and restore healthy function in a frontotemporal dementia model.

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Otago Community Trust (Funder)

Parallel lives: Uncovering shared immune pathways in placentation and cancer

Principal investigator: Dr Erin Macaulay, Department of Pathology, Dunedin School of Medicine, University of Otago

Co-investigators: Dr Silke Neumann, Assoc Prof Sharon Pattison, Jackie Ludgate, Department of Pathology, Dunedin School of Medicine, University of Otago

The placenta is a temporary organ that supports pregnancy by growing into the uterus and avoiding rejection by the mother’s immune system. Interestingly, tumours use similar strategies to grow and spread, but in an uncontrolled and harmful way. This project studies how the placenta controls immune responses, using stem cells that can develop into key placental cell types. By comparing these cells to cancer cells, we aim to understand how both tissues avoid immune attack. Our findings could reveal new ways to help the immune system fight cancer, by learning from the placenta’s natural, tightly regulated defences.

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Otago Community Trust (Funder)

Immune complexity in older people

Principal investigator: Prof Roslyn Kemp, Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago

Co-investigator: Dr Kirsten Ward-Hartstonge, Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago

As we age, our immune system loses some of its function. This loss of function is compounded in those with poor nutrition. Using new technologies, our lab will study the immune response from the blood of elderly healthy people and compare their responses to those of young healthy people. We will also associate any changes in the immune response with nutritional biomarkers of health from the blood of the same patients. Finally, we will compare the response of healthy aged people with that of colorectal cancer patients, who are not often compared to an appropriately age-matched control population.

Mactodd Community Charitable Trust (Funder)

Longer-term access to automated insulin delivery for Māori and Pacific adults

Principal investigator: Dr Alisa Boucsein (Research Fellow), Department of Women's & Children's Health, Dunedin School of Medicine, University of Otago

Co-investigators: Prof Ben Wheeler, Department of Women's & Children's Health, Dunedin School of Medicine, University of Otago & Associate Prof Ryan Paul, Te Huatakia Waiora School of Health, University of Waikato

Type 1 diabetes (T1D) is one of the most common chronic diseases diagnosed in childhood and cannot be cured; therefore, people with T1D must incur considerable burden intensively managing their blood sugar levels for the rest of their lives. Advanced diabetes technology that can improve health outcomes and reduce burden of care is available in New Zealand, however, due to a number of reasons Māori and Pacific adults are less likely to receive funded insulin pumps or have access to modern blood sugar monitoring systems. Our goal is to improve access to this advanced technology for Māori and Pacific adults, and thereby to guarantee more equitable health outcomes.

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Friends of the Foundation (Funder)

Exploring the Link Between Infertility and Ovarian Cancer

Principal investigator: Assoc Prof Megan Wilson, Department of Anatomy, University of Otago

Co-investigator: Bridget Fellows (PhD student), Department of Anatomy, University of Otago

Ovarian cancer is a serious health issue in Aotearoa, especially affecting Māori and Pacific women. Our research focuses on a protein called LHX9, crucial for ovarian health. We aim to understand how reduced levels of LHX9 contribute to ovarian cancer and infertility. We will use advanced techniques to study gene activity in mouse ovaries to uncover early changes leading to cancer. Our findings will help identify new strategies for prevention and treatment, offering hope for better health outcomes in high-risk communities.

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Healthcare Otago Charitable Trust (Funder)

Assessing HRD: A pathway to personalized PARPi therapy in ovarian cancer patients

Principal investigator: A/Prof Magdalena Ratajska, Department of Pathology, University of Otago

Co-investigators: A/Professor Tania Slatter, A/Professor Heather Cunliffe, Department of Pathology University of Otago, Dr Simone Petrich Department of Surgical Sciences, University of Otago

When faulty, homologous recombination (homologous recombination defect, HRD) does not allow for accurate DNA repair, and cells accumulate further mutations. Importantly, HRD is present in different tumours, including ~50% of ovarian cancers. HRD cells are sensitive to specific drugs, such as PARP.

inhibitors (PARPi), which block DNA repair enzymes, leading to cell death and thus, great clinical value. However, prolonged PARPi therapy may result in the development of some blood cancers; therefore, it should be given to patients whose benefit from therapy outweighs potential side effects. Therefore, we aim to rigorously evaluate the clinical value of two available HRD tests for prognostication in ovarian cancer patients.

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Aotearoa Gaming Trust (Funder)

An exercise in brain health: how does exercise liberate neurotrophic factors?

Principal investigator: Dr. Kate Thomas, Department of Surgical Sciences, University of Otago

Co-investigators: Dr Travis Gibbons, Northern Arizona University, USA, Prof Cliff Abraham Psychology Department, University of Otago, Prof Phil Ainslie, University of British Columbia, Canada

The number of New Zealanders living with dementia is expected to double by 2050. With no effective treatments available, we need interventions that delay the onset of neurocognitive decline. Exercise promotes the release of brain-derived neurotrophic factor (BDNF), a key protein that maintains brain function. We have unique methods that allow us to characterise the production of BDNF and its movement in circulation into, out of and across the brain in response to high-intensity exercise in young, healthy adults. This insight will improve understanding of the potential of exercise to maximise BDNF availability and therefore improve healthy brain ageing.

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Aotea Group Holdings Limited (Funder)

Activins: promising prognostic markers for prostate cancer

Principal investigator: Dr Karen Reader, Department of Pathology, University of Otago

Current methods for diagnosing prostate cancer can not accurately predict whether patients with moderate grade tumours require treatment (radiotherapy or surgery) or can be safely monitored. We have shown that the levels of two proteins (activin B and activin C) in prostate cancer biopsies are related to the tumour grade. The aim of our research project is to confirm if these proteins can be used to distinguish between moderate Gleason grade tumours and higher-grade tumours in patient samples from Dunedin. This could lead to the development of a more accurate test to help clinicians and patients decide between treatment and active surveillance.

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Otago Community Trust (Funder)

Identifying and assessing cellular immunity to measles after inhaled MMR vaccine

Principal investigator: Melanie Millier (Research Fellow), Department of Women's & Children's Health, Dunedin School of Medicine, University of Otago

Co-investigators: Prof. James Ussher, Department of Microbiology & Immunology, University of Otago and Professor Peter McIntyre Department of Women's & Children's Health, Dunedin School of Medicine, University of Otago

In Auckland’s 2019 measles outbreak, young adults made up ~1/3 of total cases, with ~14% previously vaccinated with measles-mumps-rubella (MMR) vaccine. Waning of antibodies since childhood vaccination increases the risk of future outbreaks from introduced cases. Cellular immunity is less understood in young adults with low antibodies but likely contributes to measles immunity in parallel with antibody production. The Otago-led ‘MAXXED’ clinical trial is currently investigating new ways of giving MMR vaccine, including an inhaled mist. An internationally unique opportunity exists to include cellular immunity investigations to the antibody testing. Findings will be novel, while contributing to a more complete understanding of measles immunogenicity following inhaled MMR vaccine.

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Otago Community Trust (Funder)

The immune cell landscape enabling a novel intervention in inflammatory bowel disease

Principal investigator: Dr. Nicholas Fleming, Department of Pathology, University of Otago

Co-investigators: Assoc. Prof. Anita Dunbier, Department of Biochemistry, Prof. Michael Schultz, Department of Medicine, Mr. Gregory Gimenez, Department of Pathology, University of Otago

Inflammatory bowel disease (IBD) is a significant and growing health burden for Aotearoa/New Zealand, which currently affects at least 20,000 Kiwis. IBD patients have a limited range of treatments available, which they vary greatly in response to. Recently, a new and promising drug has been developed that has potential to cooperate with existing options and allow more patients to control their disease. However, this new combination treatment may only work for some people. Here, we will test a novel combination treatment as well as a genetic marker that we propose will predict response to the therapy.

ADEPT MACTODD Charitable Trust (Funder)

Cracking the secrets of senescence to reveal mechanisms of ageing and disease

Principal investigator: Dr Erin Macaulay, Department of Pathology, University of Otago.

Co-investigators: Dr Chi Lynch-Sutherland, Children’s Medical Research Institute, Sydney, NSW, Australia, Dr Xaviour Walker, Department of Medicine, University of Otago.

As we age, our cells undergo a process where they stop dividing and release harmful signals. This process is called senescence and plays a key role in ageing and age-related diseases like cancer and heart disease. With the increasing number of ageing individuals and rising prevalence of age-related conditions, understanding the mechanisms behind senescence is urgent. Our research focuses on a genetic disorder where cells avoid senescence and form tumours. By studying senescence in these cells, we aim to uncover its secrets and develop novel strategies and treatments that promote healthy ageing and alleviate the burden of age-related conditions on our healthcare system.

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Aotea Holdings Group Limited (Funder)

Breaking up free living sedentary time in the evening with regular activity breaks: A feasibility study

Principal investigator: Dr Meredith Peddie, of Human Nutrition, University of Otago

Prolonged periods of sitting in the evening, and sleeping for less than 7 hours a night, are both associated with an increased risk of developing several diseases, such as heart disease and type 2 diabetes. Our group was among the first to show, in a laboratory setting, that regularly interrupting prolonged periods of prolonged sitting with brief bouts of activity in the evening improved blood sugar uptake, and sleep duration both of which can reduce the risk of developing these diseases. To date, no study has investigated whether people would be willing to break up their sitting time in the evening as part of everyday life. Therefore, this study will explore the feasibility of interrupting sitting time in the evening with body weight resistance exercises in a real-life setting.

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Aotearoa Gaming Trust (Funder)

Investigating genomic alteration in tumour cells under the pressure of anti-tumour immune responses

Principal investigator: Dr Kunyu Li, Department of Pathology, University of Otago.

Co-investigators: Prof Antony Braithwaite and Prof Mike Eccles, Department of Pathology, University of Otago.

Despite the recent success of some cancer treatment strategies, most cancer patients develop cancer reoccurrence after the initial response to the treatments. There is evidence suggesting that these cancer cells had mutated, adapted, and resisted to the treatments in order to survive. In this research, we aim to understand how immune response might influence the mutation of cancer cells that allows them to develop resistance to subsequent killing by the immune system, using an animal model of melanoma. The findings of this research contribute to the improvement of treatment outcomes for cancer.

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OceanaGold (Funder)

A neuroendocrine role for GIP in the treatment of obesity

Principal Investigator Dr. Alexander Tups, Associate Professor, Department of Physiology, University of Otago

Co-investigator Dr. Geke Aline Boer, Research Fellow, Department of Physiology, University of Otago

The prevalence of obesity is increasing worldwide and is associated with serious health problems and mortality. An important cause of obesity is an imbalance between energy intake through food consumption and energy expenditure. Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut when we consume food and there are indications that GIP may signal through regions of the brain to influence food consumption and metabolism. Using a genetically modified mouse model, we will determine how GIP signals in the brain to help maintain a healthy energy balance. Results of these studies will aid future development of obesity therapies.

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Otago Community Trust (Funder)

Understanding the host immune landscape of bacterial skin infections

Principal investigator: Dr Daniel Pletzer, Department of Microbiology and Immunology, University of Otago.
Co-investigators: Dr Rajesh Lamichhane & Dr Sam Taylor Wardell, Department of Microbiology and Immunology, University of Otago.

The skin is the body’s defence barrier that protects from physical and chemical damages as well as prevents the entry of infectious agents. Damage to skin integrity can result in various skin diseases caused by bacterial microorganisms. In addition, the presence of different types of bacteria at the same time can lead to more severe infections that make effective treatment difficult. Our study will investigate small changes in host immune cells in response to individual and mixed bacterial infections to understand how the presence of one or more bacterial species alter the host immune response.

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Otago Community Trust (funder)

Targeted use of combination treatments in inflammatory bowel disease

Principal investigator: Dr Nicholas Fleming*,* Department of Pathology, University of Otago.

Co-investigator: Prof. Michael Schultz Department of Medicine, University of Otago.

Inflammatory bowel disease (IBD) is a significant and growing health burden for Aotearoa/New Zealand, which currently affects at least 20,000 Kiwis. IBD patients have a limited range of treatments available, to which they have greatly varying responses. Recently a new group of potentially useful medications was discovered, but it is expected that they may need to be combined with existing options to be effective. Moreover, evidence suggests that they may work in some patients but not others due to a common genetic variation within our population. In the supported work, we established that the genetic variation alters the severity of IBD, and then we established that one of the candidate drugs worked better than another in this setting. Going forward, these findings will help us definitively test the drugs in combination with existing treatments and will help us better understand IBD.

ADEPT MACTODD Charitable Trust (Funder)

Novel, cost effective solutions for equitable tumour mutational burden testing in NZ

Lead Researcher: Dr Robert Day, Department of Biochemistry, University of Otago

Cancer is New Zealand’s biggest killer and targeting effective therapies to patients who are likely to benefit will improve outcomes. The number of DNA changes in a tumour can predict how well a person will respond to therapies that induce the patient’s own immune system to attack the cancer. Current genomic profiling methods used to estimate mutational changes are costly, time consuming and inaccessible to many New Zealanders. This project successfully adapted technology that will make measurement of DNA changes more accessible and inexpensive. The study also generated evidence suggesting that this approach has the potential to facilitate improved and equitable cancer care.

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Aotea Holdings Group (Funder)

Using carbon monoxide to prevent doxorubicin-induced cardiotoxicity

Lead Researcher: Dr Abigail Bland, Pharmacology & Toxicology, School of Biomedical Sciences, University of Otago

Doxorubicin remains one of the most commonly used chemotherapies for cancers, including triple negative breast cancer. Although doxorubicin provides effective cancer treatment, it can inadvertently produce severe heart damage. However, reducing the dose or discontinuing treatment risks accelerated tumour progression and premature death. As low doses of carbon monoxide have been shown to be cardioprotective, this project will explore a safe carbon monoxide-releasing molecule to prevent heart damage from doxorubicin.

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Margaret Begg Charitable Trust (Funder)

How does mutation of cytochrome C cause low platelets?

Lead Researcher: Associate Professor Elizabeth Ledgerwood, Department of Biochemistry, University of Otago

Platelets are small blood cells that are essential for clotting and repair of damaged blood vessels. When people have low platelets (e.g. following chemotherapy) they require platelet transfusions. Because donated platelets have a short shelf life, scientists worldwide are trying to develop new ways of producing platelets. This requires us to fully understand how platelets are normally made. Studying people with inherited low platelets helps us understand how human platelets are made. We have identified NZ families with mutations that cause low platelets. We will determine how these mutations change platelet production. By enhancing our understanding of platelet formation, we will help international efforts identifying new therapeutic approaches for treating low platelets.

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Aotearoa Gaming Trust (Funder)

Switching from tolerance to resistance: are ncRNAs the missing link?

Lead Researcher: Dr Glen Reid, Department of Pathology, Dunedin School of Medicine, University of Otago

Cancer treatment has been revolutionised by targeted therapeutics which act by blocking the pathways that drive cancer. However, despite initial dramatic results, relapse is inevitable and a major clinical problem. Recent studies have identified a rare population of drug-tolerant cells as being largely responsible for relapse. These cells evade therapy and become permanently resistant by acquiring mutations. Here we will determine how drug-tolerant cells gain the mutations which allow them to permanently evade therapy. By understanding how drug-tolerant cells become permanently resistant our long-term goal is to prevent their contribution to relapse and improve treatment outcomes for cancer patients.

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OceanaGold (Funder)

Role of a cytochrome oxidase in making Pseudomonas aeruginosa tolerant to antibiotics

Lead Researcher: Professor Iain Lamont, Department of Department of Biochemistry, University of Otago

Pseudomonas aeruginosa is an extremely problematic bacterial pathogen, causing a wide range of infections. Antibiotics often fail to eradicate the bacteria. During infections P. aeruginosa often exists under conditions where little or no oxygen is present. We have identified a protein that helps the bacteria to resist a key antibiotic, tobramycin, during growth in the absence of oxygen. In this research we will investigate how this protein helps the bacteria resist tobramycin. The research could lead to more reliable methods for predicting which antibiotics will be effective in treating Pseudomonas infections, and in the long-term much-needed new tools for treatment.

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Otago Community Trust (Funder)

A NZ family to reveal pathways of B-cell immunity and cancer

Lead Researcher: Professor Ian Morison, Department of Pathology, Dunedin School of Medicine, University of Otago

Naturally occurring genetic variants within families provide an opportunity to reveal the pathways of human disease. We are studying a NZ family with Otago members who have a specific genetic mutation that predisposes them to autoimmune destruction of their own platelets, but also appears to predispose them to cancers of the immune system. Two members of the family have, at a young age, developed cancers of immune cells. While mouse experiments have shown disturbed immune cell development, humans are different and this family provide an opportunity to determine the role of the affected gene (MYB) in human health and disease

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Otago Community Trust (Funder)

Development of a dual action molecular targeting construct for the treatment of ADPKD

Lead Researcher: Professor Mike Eccles, Department of Pathology, Dunedin School of Medicine, University of Otago

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited fatal diseases in humans, affecting about 1 in 1000 people. Multiple members of one family can be afflicted, with devastating consequences. Tolvaptan is the only available treatment for ADPKD, although it has severe side-effects. We, and others, have shown that lowering the expression of certain genes that promote cyst growth can slow disease progression. In this proposal we will test a molecular approach that targets two of these gene products at once, PAX2 and miR-17. Developing ADPKD-specific treatments is the key to slow cyst formation and delay kidney failure.

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Otago Community Trust (Funder)

Examining the relationship between epicardial fat and heart health of post- menopausal women

Lead Researcher: Dr Hamish Aitken-Buck, Physiology, School of Biomedical Sciences (BMS), University of Otago

The thickness of fat surrounding the heart and the risk of heart disease both increase markedly in women after menopause. How changes in heart fat might contribute to heart disease processes is unknown. Using human samples, this project aims to determine whether fat deposits and formation of scar tissue within the hearts of post-menopausal women is linked to differences in fat metabolism and expression of pro-scarring factors within heart fat. The insights gained from this research will fill important gaps in the understanding of why a woman’s heart becomes more susceptible to disease after menopause.

ADEPT MACTODD Charitable Trust (Funder)

Circulating microRNAs as prognostic indicator of ischemic heart disease

Lead Researcher: Associate Professor Rajesh Katare, Department of Physiology, University of Otago

In patients with chronic heart disease, the transition from a clinically stable disease to an acute life-threatening event remains unpredictable. Echocardiography is used to determine changes in cardiac function that requires patients visiting a specialty centre, which is expensive and infrequent. Our on-going clinical study identified micromolecules released by the diseased heart into the circulation. We aim to complete the first five-year follow-up study to determine whether changes in the level of these circulating micromolecules correspond to changes in cardiac function, as measured by echocardiography. If these blood micromolecules indicate heart disease, patients can be tested frequently by their local doctor to monitor progression of disease and their response to treatment.

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Aotea Holdings Group (Funder)

Bacterial products that can improve anti-tumour immune responses

Lead Researcher: Professor Roslyn Kemp, Department of Microbiology & Immunology, University of Otago

The immune response is an important mechanism for destroying tumours. In cancer patients, a high number of T cells in the tumour is associated with positive patient outcomes, and immune therapies that improve T cell function have increased patient survival. The function of T cells, and T cell mediated therapies, have been linked with microbial communities. One proposed mechanism for improved T cell function is via microbial molecules called short chain fatty acids (SCFAs). Our research will focus on SCFAs produced by bacteria, and how they can change T cell function. We will test the ability of T cells to produce anti-tumour proteins as well as their ability to directly kill tumour cells. Our work is designed to find new ways to improve immune therapies.

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Aotearoa Gaming Trust (Funder)

BARD1: a valuable new marker to predict the outcome of triple-negative breast cancer patients

Lead Researcher: Dr Magda Ratajska, Department of Pathology, University of Otago

Drugs targeting specific mutations improve patients' outcome in several cancer types, including breast cancer. Women with triple-negative breast cancer (TNBC) do not express HER2 or estrogen/progesterone receptors, therefore they are unable to benefit from hormonal or targeted therapy. However, TNBC is more common in patients with BRCA1 mutations and they respond well to PARP inhibitor drugs (PARPi). Patients with mutations in other genes, like BARD1, can also benefit from PARPi. Here, we will characterize TNBCs with BARD1 alterations and explore the molecular features associated with patient survival. This research might help in identifying the population of patients with the greatest potential benefit from PARP inhibitor.

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Margaret Begg Charitable Trust (Funder)

Repeating the past: a role for early developmental genes in malignancy

Lead Researcher: Dr Erin Macaulay, Department of Pathology, University of Otago

Genes that promote life may also drive death. We have discovered a unique set of genes in melanoma (a dangerous skin cancer) that are also expressed in tissues of early human development. Our recent data shows that these “early developmental” genes become reactivated in melanoma, and potentially other cancer types. Importantly, these genes are not expressed in any other healthy adult tissue, so we could target them specifically in the cancer cells. This would greatly reduce side effects for patients, because their healthy cells won’t be affected. Therefore, these genes may be useful as new melanoma therapies, which are desperately needed in New Zealand.

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OceanaGold (Funder)

How does lack of oxygen increase antibiotic resistance in Pseudomonas aeruginosa?

Lead Researcher: Professor Iain Lamont, Department of Biochemistry, University of Otago

Pseudomonas aeruginosa is an extremely problematic bacterial pathogen, causing a wide range of infections. Antibiotics often fail to eradicate the bacteria. During infections P. aeruginosa often exists under conditions where little or no oxygen is present. We think this is one reason why antibiotics don’t work properly. In this research we investigated how well Pseudomonas tolerates two key antibiotics, tobramycin and colistin, when oxygen is not available. Our results showed that less tobramycin gets into the bacteria, making this antibiotic less effective, when the bacteria grow in the absence of oxygen. The effectiveness of colistin was unchanged when the bacteria were deprived of oxygen. The research could lead to better tools for predicting which antibiotics will be effective in treating Pseudomonas infections, and for improving patient treatment through co-administration of oxygen with antibiotics.

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Otago Community Trust (Funder)

Rurality, deprivation and ethnicity: their intersection and impact on health

Lead Researcher: Associate Professor Gabrielle Davie, Department of Preventive and Social Medicine, University of Otago

Unfair differences in health between socioeconomic and ethnic groups exist in NZ. It is currently less clear whether similar rural-urban differences exist and whether poor health outcomes can be explained by the socioeconomic and ethnic composition of rural areas. Obtaining clarity on this is essential to appropriately informing health policy, planning, and the delivery of health services in rural areas. Using a recently completed and robust method of classifying areas as rural or urban, this research will examine the overlap between ethnicity, socioeconomic deprivation and rurality and the influence that these factors have on health outcomes and inequities.

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Otago Community Trust (Funder)

Breast milk nutrient composition in healthy mother-infant pairs

Lead Researcher: Dr Lisa Daniels, Department of Medicine, University of Otago

Despite breast milk being the main food for 69% of babies until about 8 months of age, we don’t currently know how much breast milk they are consuming, or what the nutrient composition is, which makes it challenging to understand what intakes are required for health. In our First Foods New Zealand study, we are investigating how much breast milk New Zealand babies are consuming; this application is an extension of this work to determine the related nutrient composition of that breast milk from mother-infant pairs. Combining these novel data will yield new understanding about nutrient intakes at this very important time of life.

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Otago Community Trust (Funder)

Developing Better Therapies for Metastatic Oestrogen Receptor Positive Breast Cancer

Lead Researcher: Dr Anita Dunbier, Department of Biochemistry, University of Otago

Over three quarters of breast cancer patients diagnosed in New Zealand present with hormone-sensitive disease and are treated with anti-oestrogen therapy. Unfortunately, many develop resistance to this therapy and spread to other parts of the body leading to significant loss of life. Better treatments for these patients are urgently needed. Our previous work suggests that anti-oestrogen therapy may make tumours more responsive to treatment that stimulates the immune system. We plan to test whether immune therapies in combination with anti-oestrogen therapy can be effective against cancers that have metastasised to other parts of the body.

JN Lemon Charitable Trust (Funder)

Streaming before dreaming: how do electronic media influence sleep in children?

Researcher: Professor Rachael Taylor, Department of Medicine, University of Otago

Using electronic media before bed leads to poor sleep, which in turn, impacts how well children function the following day. We don’t currently know how much children are using electronic media in the evening (including after “lights out”), whether more interactive behaviours like gaming are worse than reading a book on your iPad, or whether using multiple devices at the same time have different effects on sleep in 10- 12 year old children. By using wearable and stationary cameras to objectively measure screen behaviours, we will be able to answer these questions, providing much-needed information for developing appropriate sleep health guidelines.

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Aotea Holdings Group (Funder)

How much breast milk are New Zealand infants actually getting?

Researcher: Dr Lisa Daniels, Department of Medicine, University of Otago

Surprisingly little is known about what infants consume during their remarkable journey from drinking a 100% milk diet at birth, to eating the same foods as their family around their first birthday. In fact, even though breast milk is the main food for 69% of New Zealand babies until at least 8 months of age, we don’t even know how much breast milk they are consuming. The First Foods New Zealand (FFNZ) study has been funded by the HRC to find out what and how New Zealand babies are being fed, but additional sample collection is required for accurate measurements to be made of the amount of breast milk babies are getting. This funding will enable FFNZ to collect these data.

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Otago Community Trust (Funder)

Does "Closing the Loop" improve sleep in those living with type 1 diabetes?

Researcher: Associate Professor Ben Wheeler, Department of Women’s & Children’s Health, University of Otago

People living with Type 1 Diabetes need to ensure their blood glucose is well controlled to avoid short and long-term complications. New technology (undergoing clinical trials) acts like an artificial pancreas to do this. Our preliminary evidence that sleep improves using this technology will be explored further in a new trial of 60 patients; measuring and asking about their sleep, alongside interviewing a subsample about their experiences using this technology specifically related to glucose management and everyday living. The research will provide important information on the benefits of this state-of-the-art technology for improving sleep with wide implications for overall health.

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Otago Community Trust (Funder)

The Role of the Epithelial Sodium Channel (ENaC) in Breast Cancer Metastasis

Researcher: Fiona McDonald, Department of Physiology, University of Otago

Breast cancer is the leading cause of death in women worldwide, with 90% of these deaths attributed to metastasis, the process whereby cells from the primary tumour migrate and invade a secondary site in the body. Our preliminary data has suggested that the epithelial sodium channel (ENaC), an ion channel with a role in the regulation of blood pressure, has a significant impact on key metastatic characteristics. Our research investigates the role ENaC may play in metastasis with a particular focus on how ENaC affects the speed of growth of breast cancer cells.

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Margaret Begg Charitable Trust and Friends of the Foundation (Funder)

Understanding and targeting drug tolerance in lung cancer to prevent drug resistance

Researcher: Dr Aniruddha Chatterjee Department of Pathology University of Otago

Cancer drugs that target specific mutations have improved survival for some patients, but responses are usually short-lived and patients invariably suffer relapse with drug-resistant tumours. Previously it was thought that this was due to traditional Darwinian selection of pre-existing mutant cells. However, recently it has been discovered that some cancer cells in a tumour are able to ‘epigenetically’ adapt to a drug-tolerant state. These persistent cells then give rise to mutants during continued treatment. Whether they exist prior to treatment, are induced by the drug, or both, is not well understood. Here we have analysed the epigenetic characteristics of these cells to better identify and target them. These results provide strong evidence that drug-tolerant cells have a distinct epigenetic signature. Future work will be aimed at determining the causal role of this signature in the acquisition of the drug-tolerant phenotype and how these might be exploited clinically.

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The Southern Trust (Funder)

Host response to mono- and polymicrobial infections in a mouse skin abscess model and treatment with an immunomodulatory peptide

Researcher: Dr Daniel Pletzer, Department of Microbiology & Immunology University of Otago

Infectious diseases have traditionally been associated with individual microorganisms. However, recent progress in sequencing technologies revealed that many infections are mixed where two or more species of microbes occupy the same niche. This increases the severity of the infection and complicates treatment strategies. It is important to understand how the body reacts to individual and mixed infections to identify better interventions for complex infectious diseases. Our research will address this gap, investigating the response of a mouse host to various infections and we will investigate a novel treatment strategy, based on a small synthetic peptide, for mixed infection.

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ADEPT-MACTODD Trust (Funder)

Delivery of a micro RNA based nanoncomposite powder for treatment of Chronic Obstructive Pulmonary Disease

Researcher: Dr Shyamal Das, School of Pharmacy, University of Otago

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. In New Zealand, it has the highest mortality of all respiratory diseases and is highly prevalent in Māori. However, current treatment of COPD has only limited efficacy. The aim of this project was to develop a novel gene therapy for COPD using an inhaled treatment. We produced formulations containing a combination of molecular regulators and tested them in the lab. This type of gene therapy has the potential to revolutionise the treatment of COPD.

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OceanaGold/Otago Medical Research Foundation (Funder)

Immunity to measles in immunised young adults - is it waning and does it matter?

Researcher: Professor Peter McIntyre, Department of Women’s & Children’s Health University of Otago

Measles is so infectious that despite high vaccination outbreaks can occur when the virus comes in from overseas – as seen in NZ in 2019 with over 2,000 cases. All commencing health science students at Otago have blood tests and more than 20% have low antibodies to measles or mumps needing a 3^rd dose of measles-mumps-rubella vaccine (MMR3). But we don’t know how accurate routine blood tests are or how well MMR3 protects young adults. In this study, we sent blood to a specialised reference laboratory in the Netherlands for more sensitive antibody tests, not available in New Zealand, before and after MMR3. Of 45 students with measles antibody below the Dunedin cut-off, only 8 (17.4%) were also low on the more sensitive reference test – but even this test missed 3/10 low results compared with a third “best in show” test. Importantly, no student who was low on more sensitive tests was missed by the cut-offs used in Dunedin. After receiving MMR3, 32 (94%) had antibody levels above the Dunedin cut-off and the other two were above the cut-off on the specialised Netherlands assay. All mumps negatives responded strongly. Conclusion: Although not as sensitive as more specialised tests, testing at Otago identified all students needing MMR3 and antibody responses to measles and mumps post MMR3 were very good.

In May of 2020 the Foundation committed funding to an urgent, fast-tracked fund specifically for COVID-19 medical research. In these extraordinary times, we responded rapidly to the need for research in this area with a single round of grants and have used a truncated application and review process for awarding funds.

T cell responses in COVID-19

Researcher: Professor James Ussher, Department of Microbiology and Immunology, University of Otago

Understanding the immune response to SARS-CoV-2 infection, the cause of COVID-19, is critical for understanding protection against reinfection and for vaccine design. In this study we evaluated T cell responses to SARS-CoV-2 in patients who had recovered from COVID-19. Blood, collected at various time points post infection, was stimulated with fragments of different SARS-CoV-2 proteins. T cell responses to these SARS-CoV-2 protein fragments were measured in a range of assays. T cell responses were most commonly seen against the spike, nucleocapsid, and matrix proteins of SARS-CoV-2. Antibody levels correlated well with CD4+ T cell responses but only weakly with CD8+ T cell responses. CD4+ and CD8+ T cell responses did not correlate. Immune responses waned over time. This suggests that antibody levels measured within 3-4 months of infection can be used as a proxy for CD4+ but not CD8+ T cell responses against SARS-CoV-2. Furthermore, nucleocapsid and matrix proteins are common targets for immune responses and could be included in second generation vaccines.

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Development of a SARS-CoV-2 spike protein pseudovirus assay

Researcher: Professor Alex McLellan, Department of Microbiology and Immunology, University of Otago

We developed a genetic construct ('pseudovirus') to assist with testing sera from vaccinated individuals and from recovered COVID-19 patients. The project generated and tested a safe (non-replicating and non-virulent) model virus that will assist with our understanding of the interaction of the SARS-CoV-2 virus with human cells. The construct will be used in the testing of human exposure to the virus, as well as in the discovery of novel anti-viral drugs.

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The impact of SARS-CoV-2 infection on human neurons

Researcher: Dr Indranil Basak, Department of Biochemistry, University of Otago

The global COVID-19 pandemic continues to have a devastating impact on our lives. Millions of patients have died with various complications. Although lung infections primarily account for the most serious outcomes, a progressively increasing number of cases of COVID-19 involve neurological symptoms like loss of taste and smell, dizziness, unconsciousness, seizures, encephalitis, and stroke. The SARS-CoV-2 virus, which causes COVID-19, can attack the brain, manifesting as brain dysfunction leading to aforementioned symptoms. Hence, our aim was to investigate the impact of SARS-CoV-2 on neurons, the fundamental units of the brain, which are likely involved in the observed neurological complications. From our study, we found that the SARS-CoV-2 virus infects human neurons at a lower rate, but that low infection rate is enough to cause changes in protein expressions, which might lead to neurological symptoms.

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ADEPT-MACTODD Charitable Trust

Researchers: Professor John Reynolds, Dr Mariana Leriche Vasquez, Dr Ben Brockway, Dr Nich Cutfield
Project Title: Detecting changes in habits in rapid eye movement sleep behaviour disorder (RBD): a pilot study
Lay Abstract: One of the early signs of Parkinson’s disease (PD) is the loss of habitual movements, however it is unclear if this loss is also present in disorders associated with PD. We have developed a simple computational tool by which to detect habit loss and will test a sample of people with a condition called rapid eye movement sleep behaviour disorder (RBD). Comparison between results obtained from RBD and healthy participants with our ongoing PD study, will allow us to determine the specificity of our tool for PD and the ability to detect habit loss in a population with some association with PD.

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Mike Bird and Friends of the Foundation

Researchers: Professor Alison Heather (Physiology) & Dr Louise Bremer (SDHB)
Project Title: Serum estrogen receptor bioactivity and breast cancer risk
Lay Abstract: Breast cancer is the most frequently diagnosed cancer in women. All women are at risk of recurrence after mastectomy. The measurement of serum estradiol in these patients can be used to guide therapy and as a prognostic tool. Unfortunately, estradiol measurements have proven unreliable on both counts. In contrast, estrogen receptor bioactivity is reported to be high in women that develop breast cancer. As such, there is now considerable interest in using estrogen receptor bioassays to track breast cancer patients. We aim to measure estradiol levels and estrogen receptor bioactivity in serum of women pre and post-aromatase inhibitor treatment. If the bioassay identifies estrogen receptor bioactivity beyond that derived from residual estradiol levels, this will provide a major impetus for discovering non-classical estrogens that can drive recurrence.

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OceanaGold

Researchers: Dr. Htin Lin Aung & Thomas Devine (Microbiology & Immunology)
Project Title: Transcriptional Profiling of the New Zealand Tuberculosis Rangipo strain within macrophages
Lay Abstract: Tuberculosis (TB) is the number one cause of death from an infectious disease in the world. Elevated TB rates among indigenous peoples are a major theme in the history of worldwide TB. Despite New Zealand being a low TB burden country, the disease has a disproportionately higher incidence in Maori (six times higher) when compared to New Zealand Europeans and the causes of the disparity in TB infection between Maori and Non- Maori remain unknown. TB is a prime example of a "social disease" with the risk factors including a complex combination of human factors (obesity, diabetes, smoking and alcohol use), socio-economic factors (crowding, poverty and unemployment) and bacterial factors (strain and transmissibility). In addition, a New Zealand unique Mycobacterium tuberculosis (MTS) strain known as the Rangipo strain is highly prevalent in Maori. In this study, we will unravel the genetics of the Rangipo strain to discover its transmission characteristics compared to other strains in the Maori population.

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JN Lemon Charitable Trust

Researchers: Dr Roslyn Kemp, Paulo Urbano, (Microbiology & Immunology) & Prof Michael Schultz (Medicine)
Project Title: The control of inflammation by regulatory T cells - an immune- intestinal organoid model
Lay Abstract: Inflammatory bowel diseases (IBD) are caused by uncontrolled inflammation in the gut. This inflammation causes a breakdown in gut function, chronic pain and inflammation. Many factors are involved in both the cause and progression of IBD, including the immune system, the gut microbiome, the epithelial barrier, and the genetic background of the individual. The immune response is usually controlled by a type of immune cell, regulatory T cells (Tregs) to prevent inflammation. We plan to study the types of Tregs in people with IBD using intestinal organoids, which replicate the epithelial barrier, immune response and gut microbes from individual patients.

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The Southern Trust

Researchers: Assoc Prof Joanna Kirman & Dr James Ussher (Microbiology & Immunology)
Project Title: Improving vaccination against TB: inducing trained innate immune cells in the lungs
Lay Abstract: Tuberculosis (TB) kills more people annually than any other single infectious agent. The existing vaccine, BCG, protects children but not adults against TB. Understanding the protective immune mechanisms of the BCG vaccine is a critical first step to progress development of an improved TB vaccine that will also protect adults. This study will investigate a new idea - that the first responding immune cells (innate cells) can be trained by vaccination. We will provide the first insight into whether innate immune training is uniform across lung innate cells following BCG vaccination or whether certain innate cells are more "trainable" than others.

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Margaret Begg Charitable Trust

Researchers: Dr. Narun Pornpattananangkul (Psychology), Dr. Argyris Stringaris (NIH, USA)
Project Title: Motivation and Cognitive Abilities as Mediators between Polygenic Scores and Psychopathology in Children
**Lay Abstract:**The role that genes play in increasing the risk for mental disorders such as major depressive disorder (MDD) and attention deficit hyperactivity disorder (ADHD) becomes increasingly clear. Yet, we still don’t know what psychological and cognitive links between genetic risk and psychiatric symptoms are. Here we focus on three such links, namely:

1. how sensitive children are to negative/aversive situations;

2. how sensitive children are to positive/motivational situations; and

3. how well children are in performing cognitive-demanding tasks in general.

We found that the influences of MDD and ADHD genetic liability on psychopathology were partly explained by these three psychological and cognitive mechanisms. Accordingly, these findings suggest targets for potential preventions and interventions for children with genetic liability.

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Otago Community Trust

Researchers: Dr Louise Bicknell & Dr Karen Knapp (Pathology)
Project Title: Investigating the mechanisms of a novel genetic cause of intellectual disability
Lay Abstract: We have identified genetic alterations in 20 patients with intellectual disability in novel disease genes that serve to fit DNA inside cells. While our genetic evidence is significant, we need to understand how these alterations impact the normal functioning of the encoded protein. In particular, the association of these proteins with DNA is dynamic, and we hypothesize the efficiency of this dynamic association could be impacted by these genetic alterations, ultimately impacting normal cell functioning during brain development. Our research has the potential to gain insight into more common, complex neurodevelopmental conditions such as autism, epilepsy and developmental delay.

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Otago Community Trust

Researchers: Professor Mike Eccles, Dr Aniruddha Chatterjee, Dr Euan Rodgers (Pathology), Dr Chris Jackson (SDHB)
Project Title: A blood-test to epigenomically predict melanoma patient response to lmmunotherapy
Lay Abstract: These are exciting times for cancer immunotherapy, since after many frustrating years, immunotherapies using Keytruda, Opdivo and similar drugs have now become clinically validated and successful treatments for a number of cancer types. However, only a small proportion of treated patients actually respond to these treatments, while all treated patients frequently are susceptible to permanent and debilitating adverse drug effects. Unfortunately, no accurate predictive tests are available at present for determining who will respond to treatment. In this project we will identify markers from blood to eventually allow us to develop a convenient blood-test to predict melanoma patient response to immunotherapy.

OceanaGold

Prof Iain Lamont & Dr Kay Ramsay (Biochemistry)
The effect of sub-lethal concentrations of antibiotics on Pseudomonas aeruginosa.

The bacterium Pseudomonas aeruginosa causes severe respiratory infection for individuals with cystic fibrosis (CF). Regular and prolonged antibiotic treatment is required to maintain patients’ health. During periods of treatment P. aeruginosa within the airways are often exposed to sub-lethal amounts of antibiotics. Limited studies have shown that an increase in antibiotic resistance of P. aeruginosa can occur under these conditions, but have not examined bacteria from CF individuals or investigated the mechanisms of resistance. By exposing clinical and laboratory strains to sub-lethal amounts of clinically relevant antibiotics over an extended period we have shown that this exposure is sufficient to alter the effectiveness of antibiotic treatment. This is reflected in detrimental changes seen within the DNA of these bacterium. Understanding the genetic basis of resistance has potential for improved use of antibiotics, by using DNA testing to guide prescription. Results from this research will contribute to the knowledge of P. aeruginosa resistance, influence therapeutic choices and ultimately has potential to better the clinical outcome for patients.

Our study has shown that bacteria can develop antibiotic resistance when exposed to sub-lethal amounts of antibiotic. This finding helps to explain the emergence of antibiotic-resistant bacteria during chronic infections such as in cystic fibrosis.

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JN Lemon Charitable Trust

Dr Shyamal Das (Pharmacy), A/Prof Rajesh Katare (Physiology), Prof Phillip Hill (Preventive and Social Medicine), Dr Jack Dummer (Medicine)
**Evaluation of safety and pharmacokinetics of inhaled rifampicin in rats.
**Tuberculosis (TB) is an infectious disease primarily localized in the lung although it can affect other organs. Current oral and parenteral treatment using high doses of multiple drugs is ineffective since only small fraction of drug goes to the lung. Potentially more effective treatment can be achieved by pulmonary delivery of anti-TB drugs ensuring high levels of drugs in both lungs and blood. This is a pre-clinical study of inhaled rifampicin, a first line anti-TB drug, powder in rats to evaluate its safety and pharmacokinetics. This will enable design of clinical studies on inhaled rifampicin and other anti-TB drugs

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Southern Victorian Charitable Trust

Dr Lyn Wise & Prof Michelle Glass(Pharmacology and Toxicology (Psychological Medicine)
**Refining vascular networks through biased receptor tyrosine kinase signaling.
**Tyrosine kinase receptors are critical to the development and regeneration of any tissue in our body. Aberrant expression of these receptors has been linked to a diverse range of disorders from growth and healing defects, to pathological inflammation and cancer. This research aims to discover the mechanism behind signalling bias in these receptors. This will be the first step towards development of drugs that refine vascular networks, with the ramifications extending from the engineering of vascularised bone or skin, to therapeutic angiogenesis for ischaemic tissues, to the normalisation of retinal or tumour vasculature.

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Mike Bird and Friends of the Foundation

Dr Luke Wilson (Medicine), Prof Dirk de Ridder & Dr Sook Ling Leong (Surgical Sciences)
**Closed-loop neurofeedback on the cardiac autonomic nervous system, a pilot study.
**Alterations in the nervous control of the cardiovascular system is an independent risk factor for cardiovascular disease and is difficult to treat. We will use a brain training technique known as lnfraslow neurofeedback for two key areas of the brain that are known to positively impact the nervous control of the cardiovascular system in healthy individuals. If the findings of the infraslow neurofeedback training are positive we will attempt this form of training in patients with known alterations in the nervous control of the cardiovascular system.

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OTAGO COMMUNITY TRUST

Dr Kiel Hards & Prof Greg Cook (Microbiology and Immunology)
**How do proton-motive forces correlate with antimicrobial efficacy?
**Antimicrobials were once the “one-size fits all” approach to varied societal problems; such as controlling infections in human, animals and plants, or their extensive use as growth promoters in food animals. However, microorganisms appear to be winning the drug arms race and, without more dedicated research, they threaten to return society to a pre-antibiotic era. It’s known that all organisms produce a kind of biological electricity, usually a proton­ motive force (PMF), when they respire. Recently, it was found that short-circuiting this electricity is an incredibly effective property in antimicrobials. Our research proposes to investigate how new drugs affect the PMF in various human pathogens, focusing on the Tuberculosis bacterium.

Dr Nicholas Fleming (Pathology), Dr Peter Shepherd (Auckland University), Prof John McCall (Surgical Sciences)

A new biomarker for colorectal cancer prognosis and targeted therapy in southern New Zealand. Otago, Southland and South Canterbury have the highest rates of death due to bowel cancer in New Zealand, being approximately 25% higher than the national average. We have analysed 192 patients from these districts and identified a common and easily testable genetic feature that indicates who will get earlier and faster progressing bowel cancers. The feature has immediate value for predicting the course of the disease in southern New Zealand, but may have greater value for indicating which therapies are most likely to work, including immunotherapy. The work has now been expanded in scope due to co-funding by the HRC, and we have explored the cellular mechanisms that likely contribute to the effects of the feature. The feature may guide the successful use of this drug for bowel cancer patients in southern New Zealand.

Mike Bird and Friends

Engineering yeast as an ideal expression host for human P-glycoprotein (ABCB1)
Dr Erwin Lamping & Dr Nicholas Heng (Department of Oral Sciences, School of Dentistry, University of Otago) & Prof Richard Cannon (Sir John Walsh Research Institute, School of Dentistry, University of Otago)
P-glycoprotein (P-gp) is a very important human membrane protein. It pumps toxic compounds out of cells, but it also causes tumours to become resistant to anti-cancer drugs. Thus, we need to find inhibitors of P­gp in tumours but not in healthy cells. We plan to study P-gp in our baker’s yeast model which have other membrane protein pumps removed. This study aims to discover how we can get high levels of functional P-gp in yeast and measure the interaction of drugs with P-gp. The results of this research will be important for discovering alternative routes to treating cancer and other diseases.

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OceanaGold

Understanding the role of the brain in the onset of menopause
Dr Xinhuai Liu & Professor Allan Herbison (Department of Physiology, School of Biomedical Sciences, University of Otago)
With the continuing increase in life-span, more and more women live with menopause. Menopause women are more prone to develop diseases such as cardiovascular disease and osteoporosis. To optimize the long-term well-being of midlife women, it is necessary to elucidate mechanisms underlying the onset of menopause. In this project, we will use a mouse model to identify changes in the brain following induction of menopause and endocrine alterations.

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JN Lemon Charitable Trust

Resistance is futile: Investigating collateral hypersensitivity to combat antibiotic resistance
Dr Wayne Patrick (Department of Biochemistry, School of Biomedical Sciences, University of Otago)
This is a war, and one that humankind is losing. Microbes have now evolved mechanisms of resistance to every available class of antibiotic. Rather than focusing on the costly development of new antibiotics, this work will investigate an alternative strategy that manipulates an aspect of bacterial evolution known as collateral hypersensitivity. Evolving resistance to one antibiotic often results in increased sensitivity to others. Currently, a detailed understanding of this phenomenon does not exist. We will use high­ throughput approaches to systematically map the collateral hypersensitivity profiles of three resistant bacterial species. Ultimately, this may allow doctors to prescribe exactly the right antibiotic, every time.

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Southern Victorian Charitable Trust

Can microRNA be used as a biomarker to predict treatment response in anxiety?
Associate Professor Bruce Russell (School of Pharmacy, University of Otago), Dr Margaret Ryan (Department of Anatomy, School of Biomedical Sciences, University of Otago) & Professor Paul Glue (Department of Psychological Medicine, Dunedin School of Medicine, University of Otago)
Most medical conditions such as hypertension have an easily measureable target such as blood pressure that can be used to diagnose and measure treatment success; however, mental illnesses do not. This is mostly due to the complexity of the human brain. This project aims to find a small compound in the blood that can used to diagnose and then predict whether or not someone with severe anxiety will respond to treatment.

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Novel insights into the genetics of osteoporosis through studying the genome of a NZ family

Dr Louise Bicknell & Dr Karen Knapp (Department of Pathology, Dunedin School of Medicine, University of Otago)
Osteoporosis is a chronic skeletal disease associated with decreased bone mineral density and structural deterioration of bone architecture, affecting more than 80,000 people in New Zealand and over 200 million people worldwide. Our current understanding of the genetic causes of osteoporosis is incomplete and a better understanding of bone physiology is essential to facilitate the ongoing search for improved therapeutics for osteoporosis. We have a unique opportunity for the discovery of both novel candidate genes and new mechanisms regulating bone remodelling in osteoporosis, through studying a New Zealand family in which a boy is severely affected by syndromic juvenile osteoporosis. Through studying the genome of this New Zealand family, we have the potential to discover novel insights into the genetics of osteoporosis.

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Infraslow neurofeedback for food craving in overweight and obese women, a pilot study

Professor Dirk de Ridder & Dr Sook Ling Leong (Department of Surgical Sciences, Dunedin School of Medicine, University of Otago) & Associate Professor Patrick Manning (Department of Medicine, Dunedin School of Medicine, University of Otago)
There are several areas in the brain related to reward processing that encourage overeating. Brain imaging studies have shown that certain patterns of brain activity seen in overweight and obese individuals are similar to those shown in addiction. One implicated area is called the posterior cingulate cortex (PCC), which appears to function abnormally in individuals who are addicted to food. lnfraslow neurofeedback, which utilises real time display of brain activity to allow self-regulation of brain function, may help reduce food craving in people with signs of food addiction who have abnormalities in the PCC.

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Bioenergetics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Professor Warren Tate (Department of Biochemistry, School of Biomedical Sciences, University of Otago) & Dr Lynette Hodges (School of Sport and Exercise, Massey University)
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severely debilitating unexplained illness that has a distinguishing symptom of exercise intolerance or “post-exertional malaise”. We aim to focus on this feature of the illness by addressing bioenergetic functions of the cell’s energy powerhouses, the mitochondria, in ME/CFS patients compared to healthy controls. Literature has suggested that ME/CFS patients have significantly low levels of Co-enzyme Q 10 (CoQ) and we aim to determine whether the commercial supplement MitoQ10 (developed in 2001 at the University of Otago) that targets CoQ to the mitochondria will improve energy producing functions in cells from ME/CFS patients.

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Immune cells in the stroke microenvironment – Drivers of differential outcomes in obesity?

Associate Professor Sarah Young & Dr Silke Neumann (Department of Pathology, Dunedin School of Medicine, University of Otago) & Dr Andrew Clarkson (Department of Anatomy, School of Biomedical Sciences, University of Otago)Stroke is one of the leading causes of death and long-term disability in New Zealand, with limited treatment options available. Inflammation of affected brain regions is a major complication of stroke and strongly impairs nerve cell repair and rehabilitation. Underlying medical conditions, such as obesity and diabetes dramatically increase the likelihood of experiencing a stroke and further impede the healing process. In this project, we aim to understand the role of immune cells that drive inflammation after a stroke and how these contribute to worse outcomes in obese and diabetic patients.

Zonta Club of Metropolitan Dunedin (Women’s Health)

Targeting triple-negative breast cancer stem cells with the oncolytic Seneca Valley virus
Dr Mihnea Bostina & Dr Laura Burga (Department of Microbiology & Immunology), Professor Rhonda Rosengren (Department of Pharmacology & Toxicology)
Triple negative breast cancer (TNBC) is considered the most aggressive subtype of breast cancer. Currently, there is scientific consensus that targeting cancer stem cells in TNBC would reduce multi-drug resistance, malignancy, and the relapse of disease. Tumour endothelial marker TEM8 has recently emerged as a promising stem cell marker in TNBC. We have identified TEM8 as the target for Seneca Valley Virus (SVV). This virus is being examined in several clinical trials because of its ability to infect and kill cancer cells. These types of viruses also have an ability to spread and destroy the remaining tumour. This project intends to confirm the presence of TEM8 as a cancer stem cell marker by screening a large panel of TNBC cell lines and then to evaluate the cancer killing potential of SVV.

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JN Lemon Charitable Trust

High-resolution imaging of host cell exocytosis during infection by the bacterium Listeria
Associate Professor Keith Ireton & Dr Mihnea Bostina (Department of Microbiology & Immunology)
Listeria monocytogenes is a food-borne bacterium that causes abortion or meningitis. In NZ and many other developed nations, Listeria infections result in high rates of hospitalization (-90%) and mortality (-20%). Critical for disease is the ability of Listeria to penetrate inside and replicate within human cells. How Listeria provokes human cells into ‘swallowing up’ bacteria is not understood. In this proposal, we use high resolution imaging approaches to test the novel idea that Listeria subverts a normal host process called ‘exocytosis’ in order to gain entry into human cells.

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OceanaGold & Collective Donation for Cancer

Targeting cancer using modified T cells recognising a tumour coagulation factor
Associate Professor Alexander McLellan & Dr Sarah Saunderson (Department of Microbiology & Immunology)
We will develop a new strategy for targeting solid tumours by exploiting the overexpression of a coagulation factor expressed on a number of highly invasive solid cancers that are often refractory to chemotherapeutic treatment. T cells will be genetically modified using an antibody sequence against a tumour antigen which will be spliced to intracellular T cell signalling machinery. This grant will provide proof of principle that this approach can be used to destroy cancer.

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St Joan’s Trust (Care of Elderly) & Southern Trust

Is sAPP protective against the toxicity of peptide A in Alzheimer’s disease?
Prof Warren Tate & Mrs Katie Peppercorn (Department of Biochemistry)
Sporadic Late Onset Alzheimer’s Disease (LOAD) is an increasing health, social and economic burden to New Zealand, and there are no effective therapies to reverse, or delay its onset. There is little general understanding of why some people develop the disease on ageing and others do not. Ultimately in the disease there is an increased concentration of toxic amyloid-beta (A) peptide aggregates that lead to destruction of neurones. Our studies show a neuroprotective brain protein, secreted amyloid precursor protein-alpha, (sAPP) has promise as a therapeutic agent for LOAD, as it can reverse memory loss in rats. We have preliminary data that sAPP may mediate its protective function by interacting with A, and it may also interact with the enzyme that produces A, BACE 1. Here we will investigate the neuroprotective functions of sAPP by determining whether it can reverse the aggregation of A, and interact with a specific toxic species to lower its concentration. We will determine whether sAPP interacts with the BACE 1 enzyme in vitro and can inhibit its enzyme activity. Since sAPP and A may be produced in different cellular compartments we will determine whether they are subsequently located together, perhaps in the lysosome.

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Southern Victorian Charitable Trust

Investigating the spread of extended spectrum beta-lactamase (ESBL)-producing E. coli in Dunedin
Dr James Ussher, Dr Ambarish Biswas & Dr Xochitl Morgan (Department of Microbiology & Immunology)
Antimicrobial resistance, especially amongst members of the Enterobacteriaceae family, is a rapidly evolving global emergency. In Dunedin there has been an increase in the incidence of urinary tract infections caused by multi-drug resistant Escherichia coli that produce an extended-spectrum -lactamase (ESBL). It is unknown how these ESBL-producing E. coli are spreading. In this study we will use whole genome sequencing to determine whether the Dunedin isolates represent a clonal outbreak of one or more strains, or the dissemination of a mobile genetic element. This will inform future studies to define the mode of transmission of these multi-drug resistant pathogens and any possible public health intervention.

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Visualising cerebellar driven motor learning

Associate Professor Ruth Empson (Department of Physiology)
The cerebellum is part of the brain that integrates sensory information (from sensors that tell us about our environment) with movement information (eg. where to place our foot). In fact electrical activity of the cerebellum is critical for refining and controlling movements during everyday life, yet we understand little about how the cerebellum achieves this. Here we aim to leverage our recent success using genetically encoded reporters of neuronal electrical activity to determine the nature and timing of cerebellar synaptic activity during movement. These previously impossible experiments could radically change the way we think about how we refine and control movement.

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Sorting out childhood leukaemia

Professor Ian Morison & Dr Robert Weeks (Department of Pathology)
Childhood acute lymphoblastic leukaemia (ALL), the most common childhood cancer, originates before birth. Accumulating evidence suggests that a distinct population of fetal lymphocytes might be the cell-of-origin of ALL. Childhood acute lymphoblastic leukaemia has a characteristic DNA methylation profile. We will use this profile to search for and enrich for normal lymphocytes in neonates that reflect the lineage from which ALL arises. Once isolated, this cell population will be characterised in detail and then studied to identify specific receptors and pathways that can be targeted for more effective and safer treatments.

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Development of fluorescent ligands for cannabinoid type one receptor

Dr Andrea Vernall & Associate Professor Joel Tyndall (School of Pharmacy) & Associate Professor Michelle Glass (Department of Pharmacology & Centre for Brain Research – Auckland)
Cannabinoid type 1 receptor (CB1R) is a receptor occuring at high levels in the human brain and nervous system. This receptor holds huge promise as a way to treat neuropathic and inflammatory pain, liver disease, obesity, spasticity, neurodegenerative and psychological disorders. A much greater understanding of the exact role this receptor plays in important processes in the human body is required to unlock the therapeutic potential. Currently there are few tools available to study CB1R and none with the requisite properties to enable intricate biological experiments. This project aims to develop the first fluorescent ligand for CB1R, which can be used to better understand CB1R role in disease.