Doctoral Scholarships Awarded
Each year the Foundation provides funding to support for a PhD, MD or for a Master’s degree in biomedical, clinical or population health research.
A NOVEL BRAIN IMPLANT FOR PATIENTS WITH HYDROCHEPHALUS ($131,000 - 3 years) 1221005
Dr Sang Ho Kim
Auckland Bioengineering Institute, The University of Auckland
Imagine being a parent and told that your child has an abnormal build-up of fluid around the brain (hydrocephalus), which will require neurosurgery to install a tube (shunt) to drain the excess fluid. Initially, you are relieved that there is treatment, but you are told that there is a 60% chance the shunt will block within the first two years.
The consequence of shunt blockage is a life-threatening increase in pressure inside the head. Frequent visits to the Emergency Department ensue as the signs of shunt failure are subtle and can look like the common cold. Shunt failure can only be confirmed with a brain scan. Thus, having a shunt means living in a perpetual state of anxiety, not knowing when it will fail, and being exposed to radiation every time it is suspected.
A team of engineers, neurosurgeons, and I want to remove that stress, unnecessary radiation exposure, and the likelihood of missing shunt malfunction by developing a tiny brain implant that senses and wirelessly transmits pressure measurements inside a person’s head. My project is to prove our implant is safe and suitable for the intended purpose, culminating in a first-in-human safety study.
PANCREATIC EXOCRINE INSUFFICIENCY: ADVANCING DIAGNOSIS AND TREATMENT ($131,000 – 3 years) 1221001
Mrs Kylie Russell
Dept. of Surgery, The University of Auckland
Pancreatic exocrine insufficiency (PEI) occurs when the quantity of digestive enzymes released into the small bowel is insufficient to ensure normal absorption of food. If PEI is untreated, it results in micronutrient deficiency, malnutrition, poor quality of life and reduced survival. PEI develops in 56–98% of patients following surgical resection of the pancreas (pancreaticoduodenectomy (PD)). PD is the only potentially curative treatment for head of pancreas cancer, other cancers (ampullary, bile duct and small bowel cancers), chronic pancreatitis and other non-cancerous tumours of the pancreas. The foundation of treatment for PEI is pancreatic enzyme replacement therapy (PERT); however, patients are undertreated and guidelines regarding when and what dose to commence PERT are conflicting. An international survey regarding current prescribing of PERT in patients following PD will be used to develop an education module for practitioners to address gaps in knowledge. A randomised controlled trial will establish a) whether pre-emptive, routine, treatment with PERT post PD improves nutritional status and quality of life, and b) which dose (low vs high) provides maximal benefit. The project will determine the prevalence of micronutrient deficiency post PD, which is currently unknown, and develop guidelines for clinicians regarding screening and treatment protocols. The project will also test the safety of administering PERT in patients with a compromised gut through a rodent model of PD.
IDENTIFYING THERAPEUTIC TARGETS AND BIOMARKERS ASSOCIATED WITH DISTINCT ALPHA-SYNUCLEIN POLYMORPHS ($131,000 - 3 years) 1221004
Mr Kreesan Reddy
Dept. of Anatomy & Medical Imaging, The University of Auckland
Synucleinopathies are a collective of neurodegenerative diseases characterised by lesions of misfolded α-synuclein (α-Syn) aggregates. Parkinson’s disease (PD) is the most well known synucleinopathy affecting an estimated 10 million worldwide. It is presently the fastest-growing neurodegenerative disease, with the number of patients doubling from 2.6 to 6.3 million between 1990 and 2016. Multiple System Atrophy is a less common disease that presents remarkably similar to PD in the clinic. As such, approximately 20% of patients diagnosed with PD are found to have MSA upon autopsy, with the converse occurring in patients diagnosed with MSA. At present, there are no biomarkers or disease-modifying treatments for PD and MSA. Current treatments address symptoms of disease, eventually becoming ineffective in the late stages of disease. It is thought that the shortcomings of these treatments are based on their use after significant neurological damage has occurred. The project aims to identify potential biomarkers and therapeutic targets that enable the distinction and treatment of specific synucleinopathies early in the disease. It is estimated that delaying the onset of neurodegenerative disorders by one year can reduce the number of cases by 11%; therefore, providing new therapeutic targets and biomarkers may help reduce disease burden in the future.
THE ROLE OF HYALUONAN IN HIPPOCAMPAL NEURON DEVELOPMENT ($27,000 – 8 months) 1218004 EXTENSION
Dept. of Physiology, The University of Auckland
The growth and connectivity of brain cells (neurons) is critical for normal brain development and function. Alterations to the normal development of these cells can disrupt their ability to form connections and create neural networks. Deficits in neuronal connectivity are observed in a range of neurodevelopmental disorders including autism, attention deficit hyperactivity disorder, and can induce impairments in learning and memory. However, there is limited progress in the treatment of such disorders, as the mechanisms underlying neuronal developmental and connectivity in the normal brain remain unclear. Hyaluronan is a sugar molecule expressed throughout the body and brain, which has been shown to support non-neural cell development. Evidence suggests that this sugar is expressed in the developing brain, however its specific role in brain cell development is unknown. Thus, this research will provide a novel insight into the role of hyaluronan in normal brain function, and whether disruption of hyaluronan and the extracellular matrix contributes to various neurodevelopmental disorders. Further, this study will provide information on whether targeting hyaluronan disruption is a potential therapeutic strategy to promote normal brain function.
In March 2022, the AMRF Covid-19 Relief Fund provided an additional $3,574. This was matched by a similar contribution from the University of Auckland’s Covid Hardship Fund.
AN IMMUNOTHERAPEUTIC APPROACH TO TREATING COGNITIVE DECLINE IN AGING ($131,000 - 3 years) 1220007
Mr Conor Nelson
Dept. of Pharmacology & Clinical Pharmacology, The University of Auckland
As the aged population continues to grow, new therapies are needed to prevent the predicted escalation in the number of people affected by age-related neurodegenerative diseases. Our lab has developed an antibody-based immunotherapy targeting the GluN1 subunit of NMDA glutamate receptors. These receptors are believed to be essential to the process of learning and memory, and we have previously demonstrated that treatment with these antibodies has neuroprotective and cognitive-enhancing properties in rodent models. This project takes the next step towards the development of a GluN1 antibody therapy suitable for human use. We will determine whether site-specific monoclonal GluN1 antibodies are as effective at boosting learning and memory function as our current GluN1 antibody therapy, as the predictable binding behavior of monoclonal antibodies makes them safer for clinical use. Additionally, we will be investigating whether the ability of anti-GluN1 antibodies to selectively alter signalling at NMDA receptors is able to modify the progression of Alzheimer’s disease in a transgenic mouse model. If these experiments prove to be successful, these results will contribute to the development of a new class of therapies for improving cognitive function and increasing the brain’s resilience to neurodegenerative disease.
Funded by: Gooduck Charitable Trust
MODELLING NEWBORN CARDIOVASCULAR DEVELOPMENT ($106,000 – 2 years 6 months) 1220006
Dr Robyn May
Auckland Bioengineering Institute, The University of Auckland
Preterm birth (defined as birth before 37 completed weeks of gestation) is a global burden, with over 15 million babies born prematurely each year. Babies born early are at greater risk of a range of short-term and long-term problems, including a greater risk of cardiovascular disease (CVD) in adult life. Several mechanisms linking preterm birth to the onset of CVD later in adulthood have been suggested, however, uncertainty remains about the physiological mechanism by which preterm birth is related to poor cardiovascular outcomes later in life. This project aims to address this knowledge gap using computational modelling. Computational modelling is a type of mathematical modelling that studies the behaviour of a complex system using computer simulations. In this project, we will collect data on the heart and blood vessels of newborns and develop a computational model of the cardiovascular system for both term and preterm babies and compare them to identify differences in cardiovascular physiology between newborns of different gestational ages that may predispose preterm babies to greater cardiovascular risk later in life. The findings of this project may contribute to future clinical studies that may be able to reduce these CVD risk factors for babies born early.
In March 2022, the AMRF Covid-19 Relief Fund provided an additional $7,125.
Funded by: Curtis-Tonkin Paediatric Fund
MATERNAL MENTAL HEALTH AND VACCINATION BEHAVIOURS IN AOTEAROA ($116,000 - 3 years) 1220004
Ms Sarah Kember
School of Psychology, Massey University
Over the past two centuries, vaccines have revolutionised human health, the ongoing COVID-19 pandemic a grim illustration of the dangers of uncontrolled disease. To achieve population immunity through vaccination, however, a large number of people must be vaccinated. In New Zealand, rates remain consistently lower than necessary for population immunity. Understanding drivers for low uptake is complex, but crucial to population health. One plausible cause is anxiety and depression in pregnant women and new mothers. Studies have found a strong link between psychological distress and decision-making challenges. Yet it is during the very period when 10-20% of pregnant women and new mothers experience anxiety or depression that 7 of the 15 childhood vaccines are due. Despite good reason to believe that poor mental health in pregnancy and postnatally increases the risk of missed vaccines, experimental techniques manipulating distress level, are ethically impossible. Massey University researchers will therefore test the hypothesis using sophisticated statistical analytic techniques. The study will contribute important knowledge for future interventions to increase vaccination rates by improving maternal mental health. Given misinformation circulating about vaccines and disruptions to routine immunisation programmes due to COVID-19, the need for current and relevant research has never been more pressing.
Funded by: John Jarrett Trust
TROPHOBLAST STEM CELLS AND FETAL GROWTH RESTRICTION ($128,000 – 3 years) 1219006
Dept. of Obstetrics & Gynaecology, The University of Auckland
The placenta mediates nutrient exchange between mum and baby, and its ability to do this depends on specialised placental cells called trophoblasts. Aberrant placentation and trophoblast differentiation/function are major contributors to diseases of pregnancy such as fetal growth restriction (FGR). FGR remains an important problem it has no effective treatment, in part because we do not understand why it occurs. The James lab has developed a new method to isolate trophoblast stem cells (TSC, from which all mature trophoblasts arise) directly from the placenta without culture, and this has allowed the isolation of TSCs from term placentae for the first time. This is critical to understand how TSCs contribute to pregnancy pathologies, which can only be detected clinically in late pregnancy. Isolating TSCs from normal and FGR placentae has revealed that this population are significantly (10-fold) depleted in FGR placentae, and gene expression studies suggest this is a result of reduced cell proliferation and increased cell death. This project aims to understand how functional differences in the proliferation, death, and differentiation of TSCs may contribute to the pathophysiology of FGR. This will allow us to identify potential therapeutic targets to improve the function of FGR placentae in the future.
In March 2022, the AMRF Covid-19 Relief Fund provided an additional $7,000. This was matched by a similar contribution from the University of Auckland’s Covid Hardship Fund.
RURAL: REGIONAL VS URBAN RISK OF APPENDICITIS COMPLICATIONS ($18,000 – 1 year) 1218003
Dr Brodie Elliot
Dept. of Surgery, The University of Auckland & Northland District Health Board
Appendicitis is the most common and costly emergency general surgical disease that affects children. International studies have shown that rural patients are more likely to have poorer outcomes of appendicitis. This results in distress and harm for children and their families in the form of pain, increased stay in hospital, and need for repeat invasive procedures. Despite a quarter of New Zealanders living in a rural or small center, no study has investigated whether this problem exists here. We will first interview the families of children who have undergone an emergency appendicectomy and study any common themes that prevent rural families from accessing surgical care. Using this information we will then investigate the presentation and outcomes of all children who undergo surgery for appendicitis, nationally. This research will be used to identify any common barriers faced by rural families in accessing acute paediatric surgical care and whether surgical outcomes of appendicitis are worse for children of rural families on a national scale. This will act as a platform to guide public health improvement efforts, improve rural access to healthcare and reduce the impact of this common disease on the New Zealand’s children.
PLATELET-DERIVED GROWTH FACTOR SIGNALLING IN PATIENT-DERIVED BRAIN CELLS ($128,000 – 3 years) 1219004
Dept. of Pharmacology & Clinical Pharmacology, The University of Auckland
Platelet-derived growth factor (PDGF) is a potent mitogen involved in the proliferation, migration and survival of cells, with its effect mediated via the activation of its receptors, PDGFRα and PDGFRβ, and subsequent signalling pathway. Studies have revealed evidence of its involvement in the maintenance of blood-brain barrier integrity by promoting proliferation and survival of pericytes, a mural cell type critical to vascular function. The PDGF receptors are also found in glioma cells, playing a role in tumour development and progression, especially in Glioblastoma Multiforme (GBM), the most common and malignant primary brain tumour. Preliminary data from our lab show that both pericytes and glioma cells abundantly express the PDGF receptors and have distinct signalling properties. This project aims to thoroughly characterise the PDGF signalling pathway, with emphasis on brain pericytes and GBM glioma cells. Funded by: The Edith Rose Isaacs Estate