Awarded Project grants

Project grants awarded 2012

  • 31 Dec 2012

MOLECULAR DEFECTS IN COMMON VARIABLE IMMUNE DEFICIENCY – 2112017 ($54,913 – 10 months)

A/Prof Rohan Ameratunga, Dr Klaus Lehnert, Dr See-Tarn Woon, Ms Wikke Koopmans, Dr Anthony Jordan
Dept of Virology & Immunology, LabPLUS, Auckland District Health Board

Common variable immune deficiency (CVID) is the commonest symptomatic primary immune deficiency disorder in adults and children. CVID patients are susceptible to multiple and severe infections. Serious infection episodes often require hospitalisation. Up to 90% of CVID patients do not have confirmed genetic diagnoses. Securing a genetic diagnosis can assist with patient management and expand our understanding of this disorder. We present two groups of patients that could benefit from next generation sequencing technology. Group one are seven patients from a kindred. We conclude another gene, not the commonly known mutation TACI C104R, is the cause of CVID. Group two comprises of a family with two affected siblings but asymptomatic parents and brother. The proposed whole exome sequencing project will help identify novel genes, which may be causative. We will use our knowledge of the immune response-associated molecular pathways associated with CVID to help prioritise the mutations we identify. Identifying these genes will result in much improved patient management including family studies, early diagnosis and better prognosis. In the future we will use this technology as the discovery and diagnostic tools for other primary immune deficiency disorders with undefined genetic defects.

 

POSTOPERATIVE GUT DYSFUNCTION – 1112012 ($63,500 – 18 months)

A/Prof Ian Bissett, Dr Ryash Vather
Dept of Surgery, The University of Auckland

Postoperative ileus (POI) is an important health problem which affects a considerable proportion of patients following abdominal surgery. It slows patient recovery, increases postoperative morbidity and prolongs length of hospital stay, thereby significantly impacting quality of life and patient-perceived outcomes of surgery. It also confers a significant fiscal burden on healthcare institutions, with its management in the USA alone being estimated at $US1.5 billion annually. The objectives of this research are to characterise for the first time pressure wave movement in the human large bowel peri-operatively and after tissue healing has occurred, and to investigate the therapeutic value of gastrografin in the management of POI. The use of gastrografin for POI has not been previously evaluated. The principal methodologies used will be prospective in vivo observational studies using novel fibre optic technology, and a double-blind placebo-controlled randomised trial. It is hoped that these projects will facilitate a clearer understanding of the pathophysiologic basis of POI and functional tissue healing, and appraise the therapeutic value of an economical, safe and readily available intervention.

Funded by: Gastroenterology Fund

 

WRITTEN EMOTIONAL DISCLOSURE AND SURGERY – 1112013 ($151,616 – 2 years)

Dr Elizabeth Broadbent, Prof John Windsor, Prof Andrew Hill, A/Prof Roger Booth
Dept of Psychological Medicine, The University of Auckland

Surgery is a psychological stressor, with patients’ concerns including fear of pain, death, and separation from family. Psychological stress has been shown to impair the production of cytokines involved in wound healing and to slow the healing of small experimental wounds. Psychological stress has also been associated with altered levels of pro- and anti-inflammatory cytokines and metalloproteinases involved in wound repair in surgical patients. Furthermore, relaxation exercises have been found to improve indices of wound healing and levels of fatigue following surgery. More research is needed to investigate the effects of other types of interventions on healing after surgery. There is evidence that three, 20-minute sessions of writing about personal emotional events can improve the healing of small experimental wounds, but no research has investigated the effects of expressive writing on the healing of wounds in surgical patients. This research aims to test whether written emotional disclosure can improve wound healing in surgical patients. We will randomise 90 patients scheduled to undergo abdominal surgery to either write about traumatic events or to a control group. We will measure stress, mood, cytokines, fatigue, and wound healing. This research has implications for the delivery of pre-operative care to optimise outcomes.

 

KIDNEY STEM CELLS – 1112001 ($35,499 – 1 year)

A/Prof Alan Davidson, Dr Teresa Holm
Dept of Molecular Medicine & Pathology, The University of Auckland

New Zealand has an alarmingly high rate of kidney disease and there is an urgent need to find better therapies. Regenerative medicine utilising tissue‐specific stem cells offers the potential to treat a wide range of chronic illnesses. In this study we plan to isolate and characterise renal stem cells from the mouse with the ultimate goal of testing their ability to regenerate the kidney.

Guardian Trust

Funded by: Edith C Coan Trust

 

TARGETING EXTRACELLULAR MATRIX IN PRETERM BRAIN INJURY – 1112002 ($139,105 – 2 years)

Dr Justin Dean
Dept of Physiology, The University of Auckland

Improved hospital care has increased the survival rates of babies born very premature. However, these infants have a high rate of injury to structures in the brain important for movement, which can result in cerebral palsy. Infection of the mother or baby is an important cause of preterm delivery and preterm brain injury. However, at present we do not understand how infection works to cause injury, and treatments such as antibiotics do not improve outcomes. We have recently identified a new enzyme in the brain, PH20, which is important in controlling brain inflammation induced by infection. Further, we propose that this enzyme plays a key role in preterm brain injury, and that it may be useful as a therapeutic target. This study will examine the role of PH20 in regulating brain injury following infection, and determine whether treatments that block its activity may ultimately reduce injury.

 

THE PEOPLE STUDY – ($70,000 – 13 months)

Prof Robert Doughty, Dr Mayanna Lund
Dept of Medicine, The University of Auckland

Heart failure is a common condition with high rates of hospitalisation and death. Most clinical trials involving patients with heart failure have focused on patients with poor heart pump function (low LV ejection fraction). However, the heart pump function may be normal among a significant subset of patients with heart failure. Currently, there is uncertainty regarding which patients with heart failure with preserved pump function will be at risk of dying or being readmitted to hospital. The objectives of this study are to determine which of these patients will be at risk of these events. This large-scale, multicentre international study will recruit 2500 patients with heart failure in New Zealand and Singapore. The patients will then be followed for 2 years. The study results will impact on the clinical management of patients with heart failure in New Zealand and Singapore and will lead to the development of clinical trials to test newer treatments for patients with heart failure.

 

DURATION OF ESBLPE COLONISATION – 7112007 ($139,605 – 2 years)

Dr Dragana Drinkovic, Dr Hasan Bhally, Dr Simon Briggs, Ms Helen Heffernan, Dr David Holland, Dr Susan Taylor, Dr Arlo Upton, Dr Lifeng Zhou
Microbiology Laboratory, North Shore Hospital

Extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae (ESBLPE) are common gut bacteria that have become resistant to multiple antibiotics. When a patient is known to carry an ESBLPE during a hospital admission they must be kept in isolation. Infections due to ESBLPE can be difficult to treat, and it is not known whether humans can ever get rid of ESBLPEs. This study will test for ESBLPE in patients known to be carrying an ESBLPE to see if it continues to be detected in faeces over an extended time period (two years), and thus contribute valuable knowledge for the management of ESBLPE‐colonised patients.

Funded by: The Paul Stevenson Memorial Trust

 

BIOMECHANICAL MODELLING TO EXPLAIN TOPUS FORMATION AND BONE EROSION IN GOUT – 1112008 ($117,304 – 2 years)

Dr Justin Fernandez
Auckland Bioengineering Institute, The University of Auckland

Gout is the most common inflammatory arthritis, and causes attacks of severe joint pain and also joint damage. The foot is virtually always involved, and is usually the first area to be affected by gout. Gout is strongly associated with obesity and features of wear‐and‐tear arthritis, suggesting that loading on certain joints may play a role in the presentation of this disease. This study aims to understand why gout affects certain joints. Using a number of emerging technologies including dual energy computed tomography, motion capture, foot pressure plates and highly detailed 3D computational models, we aim to answer the question, ‘is biomechanical loading or tissue stress within the foot linked to sites affected by gout?’ This study may provide evidence for the role that biomechanics plays in development of gout and provide justification for future studies assessing gait modification and foot stress rebalance as strategies in the clinical management of gout.

 

PEPTIDE TECHNOLOGY TO COMBAT BREAST CANCER – 1112003 ($67,686 – 18 months)

A/Prof Geoffrey Krissansen, Mr Glenn Bell, Ms Yi Yang
Dept of Molecular Medicine & Pathology, The University of Auckland

Novel protein technologies developed in‐house will be employed to combat breast cancer, which is the most common cause of cancer‐related death in women. Each year in New Zealand more than 2,000 women are diagnosed with breast cancer. Breast cancer growth is driven by the female sex hormone estrogen, and is blocked by anti‐hormone drugs like tamoxifen. Unfortunately, some cancers don’t respond to tamoxifen and others become resistant to its effects. The novel protein technology we have developed has the potential to overcome these problems, and will be tested for its ability to combat breast cancer.

Funded by: Sir Lewis Ross Fund

 

TRIPLE NEGATIVE BREAST CANCER – 1112006 ($119,949 – 18 months)

Dr Euphemia Leung, Prof Bruce Baguley
Auckland Cancer Society Research Centre, The University of Auckland

Breast cancer is the major malignancy in women and one of the main treatments, apart from surgery, is to block the action of the hormone estrogen. One form of breast cancer, called “triple negative”, is particularly difficult to treat. We are developing cultures of human breast cancer cells which have this triple negative characteristic and our goals are use them to understand the mechanisms involved in their resistance to therapy and to develop new strategies for their treatment.

 

CYSTEINE DELIVERY TO THE LENS – 1112005 ($126,521 – 2 years)

Dr Julie Lim, Dr Angus Grey, Prof Paul Donaldson
Dept of Optometry & Vision Science, The University of Auckland

Age related nuclear (ARN) cataract is the leading cause of blindness in the world. Despite effective procedures to restore sight, the number of people afflicted by cataracts is estimated to reach 30 million as the world’s population ages. Faced with a looming cataract epidemic, research efforts have focused on developing novel anti‐cataract therapies to prevent or delay the onset of cataract. Since ARN cataract is associated with oxidative damage to cells in the centre or nucleus of the lens, our research efforts have concentrated on enhancing the delivery of antioxidants to this region. While glutathione (GSH) is the principal antioxidant in the lens, our work in rat, human and more recently bovine lenses, suggests that the small amino acid cysteine may also be a key antioxidant in the lens nucleus. Furthermore, our identification of cysteine uptake pathways in the lens nucleus indicates that this region is capable of accumulating this antioxidant. In this research proposal, we will expose bovine lenses to high pressure oxygen to mimic the formation of a nuclear cataract. We will then use this model to trial the delivery of cysteine formulations to see if they are effective in preventing or slowing down the progression of cataracts. This rational design and testing of targeted anti‐cataract strategies has the potential to delay the onset of ARN cataract thereby reducing the need for expensive surgical intervention.

 

THE SYNAPTIC BASIS OF HUNTINGTON’S DISEASE – 1112018 ($141,154 – 2 years)

Dr Johanna Montgomery, Dr Ailsa McGregor
Dept of Physiology & Centre for Brain Research, The University of Auckland

All neurodegenerative diseases have direct or indirect effects on synapses in the brain. Therefore a major step towards understanding what goes wrong in the diseased brain is to understand how synapse function is altered by disease. In this proposal we seek to determine the source of synapse dysfunction in Huntington’s Disease (HD). Previous work on HD mouse models has shown that receptors on the surface of neurons are mis-localised, inducing changes in synapse function. Here we will focus on two synaptic proteins, bSAP97 and aSAP97, which we have recently shown can control the distribution of receptors on neurons (Li et al., 2011, J. Physiology 589, 4491-4510). We will utilise a cellular and an animal model of HD to determine whether changing the expression levels of bSAP97 or aSAP97 can rescue normal receptor distribution, and whether this subsequently rescues normal synapse function. These cellular data will identify whether a and/or bSAP97 are part of the pathological signature for HD and also whether they could be potential therapeutic targets.

 

MELANOCORTIN TREATMENT FOR OBESITY – 1112016 ($166,636 – 2 years)

Dr Kathy Mountjoy, Dr Ailsa McGregor
Dept of Physiology & Centre for Brain Research, The University of Auckland

Stress, weight gain and glucose metabolism are influenced by a group of hormones called melanocortin peptides. These peptides comprise chains of amino acids, of varying length, and are derived from one large precursor protein found in the brain and pituitary gland, called proopiomelanocortin (POMC). Special enzymes chop-up POMC to form the melanocortin peptides, according to the body’s requirement. We have developed a mouse that lacks a particular 13 amino acid melanocortin peptide called adrenocorticotropic hormone (ACTH1-13). These mice can be used to study what effects of ACTH1-13 on physiological function. The mice appear normal until they reach puberty and then they develop obesity, but not diabetes. Treatment of these obese mice with ACTH1-13 or a natural variant that is slightly chemically altered, called α-melanocyte stimulating hormone (α-MSH), reduced mouse body weight and fat mass when mice were fed a normal diet. In light of the worldwide obesogenic environment, we will now test whether obesity and diabetes in these mice is exacerbated by a feeding a high-fat diet, and whether melanocortin hormone treatment can reverse obesity while animals feed on a high-fat diet. These studies should aid the development of improved tests and treatments for obesity and type-2 diabetes.

 

AUSTRALASIAN PAEDIATRIC HEAD INJURY RULES STUDY (APHIRST) – 3112011 ($114,000 – 18 months)

Dr Jocelyn Neutze, Dr Stuart Dalziel, A/Prof Franz Babl
Kidz First, Middlemore Hospital

Many children sustain head injuries and present to emergency departments (EDs) for evaluation. Although head computer tomography (CT) identifies all important injuries, radiation from CTs can increase the risk of fatal brain and blood cancers. However, failure to quickly identify significant intracranial injury may have disastrous consequences including long-term neurological disability and/or death. This study aims to develop a pathway to assist doctors in deciding who should have a CT scan after head injury. Several evidence-based head injury clinical decision rules (CDRs) have been developed to identify patients at risk of significant head injury. None have been validated outside their original settings. We propose to prospectively validate and compare performance of the three highest quality CDRs from the United Kingdom, United States and Canada in 10,000 children presenting to 13 major paediatric EDs in Australia and New Zealand. Identification of optimal CDRs for implementation will help minimise risks of missing clinically significant intracranial injury and radiation exposure from cranial CT scans. The results will have a major impact on head injury management in children both in New Zealand and worldwide.

 

TARGETING THE HUMAN GROWTH HORMONE RECEPTOR IN estrogen receptor positive BREAST CANCER – 1112019 ($138,193 – 2 years)

Dr Jo Perry, Dr Dong-Xu Liu, Dr Stephen Jamieson, Prof William Wilson
Liggins Institute, The University of Auckland

Humans and animals born with a deficiency in the cell surface receptor for human growth hormone (hGH) have a dramatically reduced, almost absent, risk of developing cancer. Conversely, increased levels of hGH and the hGH receptor are detectable in a variety of different human cancers, including breast cancer, and this is associated with reduced survival for breast cancer patients. However, studies investigating the efficacy of inhibiting the hGH receptor for the purposes of treating cancer are limited. We will use preclinical models of human breast cancer to test the hypothesis that hGH receptor inhibition will restrict the growth of tumours, and improve response to the anti-estrogen drug, tamoxifen. A clinically available hGH receptor inhibitor will be used in this study. Thus a successful outcome has the potential for rapid translation into the clinic, with the ultimate aim of significantly impacting on treatment outcomes for breast cancer patients.

Funded by: The Hugh Green Diabetes & Breast Cancer Research Fund

 

Wnt SIGNALLING AS A LINK BETWEEN DIABETES AND ATHEROSCLEROSIS – 1112015 ($78,071 – 2 years)

Prof Peter Shepherd, Dr Brie Sorrenson
Dept of Molecular Medicine & Pathology, The University of Auckland

Atherosclerotic cardiovascular disease is a leading cause of death and risk of cardiovascular disease is greatly increased in type-2 diabetics. Despite strong evidence linking the high glucose levels observed in diabetics with atherosclerosis, the molecular mechanism linking these states remains elusive. Atherosclerosis is largely the result of lipid accumulation in the arterial wall and we have previously observed that glucose alters lipid metabolism in macrophages, which are the cells responsible for initiating atherosclerosis through the trapping of lipid within the arterial wall. We have also observed that glucose regulates the Wnt signalling pathway in macrophage cells and this study aims to determine whether regulation of Wnt signalling components by high glucose levels could be contributing to the increased rate of atherosclerosis in diabetics. We will test how glucose regulates Wnt signalling factors, such as LRP5/6 and β-catenin, and determine whether such regulation promotes lipid accumulation in cells of the arterial wall. Overall, this work will expose a mechanism by which cells sense and respond to high glucose levels and will provide important new information on the mechanisms linking diabetes with cardiovascular disease.

Funded by: Marion Ross Memorial Fund

 

OTOPROTECTION BY ADENOSINE RECEPTORS – 1112009 ($146,752 – 2 years)

Dr Srdjan Vlajkovic, Prof Peter Thorne, Dr Detlev Boison, Prof Gary Housely
Dept of Physiology, The University of Auckland

Hearing loss affects 10-13% of New Zealanders and this prevalence will increase with the aging population. Exposure to noise and drugs toxic to the inner ear are major contributing factors to this disability. Prosthetic rehabilitation via hearing aids and cochlear implants is the only current treatment for hearing loss. Hence, it is essential to develop therapies that can ameliorate or repair injury to the delicate structures of the inner ear. We have shown that hearing loss in experimental animals exposed to traumatic noise can be substantially restored by administration of drugs acting on adenosine receptors. Here we propose a set of studies that will utilise transgenic mice that lack genes for the two main types of adenosine receptors found in the inner ear to assess their responses to aging, noise stress and drug toxicity. This is critical translational research for therapeutic management of noise-, age- and drug-induced hearing loss.

Funded by: W & WAR Fraser Fund

 

IMPROVING TEAM COLLABORATION IN THE OPERATING ROOM – 1112014 ($123,626 – 2 years)

A/Prof Jennifer Weller, Prof Alan Merry, Mr Ian Civil, Ms Wendy Guthrie, Dr Craig Webster, Dr Jane Torrie, Mr Andrew MacCormick, Ms Kaylene Henderson, Dr David Cumin, Dr Matt Boyd
Dept of Anaesthesia, The University of Auckland

Recent, important studies have shown that failures in teamwork and team communication in the operating theatre (OT) lead directly to clinical errors and patient harm. Research also suggests that training as a team for those who are expected to work in teams can significantly reduce these teamwork errors. These findings form the basis of the United States Institute of Medicine’s directive that such team-based training is needed. Despite this, training in healthcare tends to occur within professional specialties (professional “silos”) rather than in genuine interprofessional teams. Simulation provides a risk-free opportunity to train teams in a realistic environment, yet simulation activities at present remain focussed on single specialities. The current project will engage complete multiprofessional clinical teams comprising surgeons, an anaesthetist, an anaesthetic technician, and theatre nurses in a highly realistic simulated OT environment. The simulated environment and scenarios developed by our group will create a “laboratory” where multidisciplinary team interactions can be systematically studied in ways not possible in the clinical OT. We will measure the effect of a full-day simulation course intervention on surgical complications in the clinical setting. Ultimately these simulations will lead to development of definitive strategies to improve performance, OT productivity, and patient safety.

 

EXECUTIVE FUNCTION IN METHAMPHETAMINE EXPOSED CHILDREN – 1112004 ($79,083 – 2 years)

Dr Trecia Wouldes, A/Prof Linda LaGasse, Prof Barry Lester
Dept of Psychological Medicine, The University of Auckland

P and Crystal Meth are street names associated with potent forms of methamphetamine that have become increasingly problematic in NZ and worldwide. Notable is the number of women using this drug during pregnancy. Yet, scant evidence is available regarding the effect it has on child development and school readiness at 4.5 years of age. This study will investigate whether prenatal exposure to methamphetamine is associated with deficits in higher order thought processes that may interfere with behaviour and learning. We will follow up children currently enrolled in our longitudinal study of 107 children born to mothers who used methamphetamine during pregnancy and 115 children born to mothers who did not to determine whether children exposed to methamphetamine have poorer developmental outcomes than non‐exposed children. Early evidence has found behavioural effects of methamphetamine exposure during infancy. In addition, our early results show that mothers who used methamphetamine during pregnancy were at higher risk of mental health problems, ongoing substance abuse problems and lower financial resources. This research will help us to determine whether the early effects of methamphetamine persist and what additional contribution a poor home environment may have for any observed learning or behavioural problems.

Funded by: A C Horton Estate Income

 

MAPPING STUDY OF PERSISTENT ATRIAL FIBRILLATION – 1112020 ($107,426 – 2 years)

Dr Jichao Zhao, Prof Bruce Smaill, Dr Nigel Lever
Auckland Bioengineering Institute, The University of Auckland

Atrial fibrillation (AF) causes rapid and chaotic activation of the atrial chambers of the heart. It impacts approximately 37,000 New Zealanders each year and the prevalence of AF in a population increases with age, with 10% of people over 80 having AF. Māori experience morbidity and mortality due to AF at a higher rate and at an earlier stage of life than the general population. AF is associated with a range of clinical conditions including hypertension, valvular disease and heart failure. AF itself is not generally life threatening, but it can cause stroke and exacerbate heart failure. Percutaneous catheter ablation is widely used to treat patients with AF. However, results for persistent AF are much less impressive due to lack of effective technique to detect and analyse AF pattens. We propose a novel approach to atrial electrical mapping in which activation will be mapped simultaneously in both atrial chambers using novel basket catheters and test it on sheep. These data will then be referred to 3D atrial endocardial surface reconstructed from magnetic resonance images (MRI) or computed tomography (CT). A suite of real-time signal processing tools will be developed so that spatio-temporal atrial activation patterns can be analysed in real time.

Image courtesy of Ambro at FreeDigitalPhotos.net

More Awarded Project grants
Awarded Project Grants 2019
Awarded Project Grants 2018
Project Grants Awarded 2017
Image courtesy of Ponsulak / FreeDigitalPhotos.netProject grants awarded 2016
Project grants awarded 2015
Project grants awarded 2014