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Investigating the role of distinct α -synuclein strains in different α -synucleinopathies JamesWiseman Supervisor: Prof Maurice Curtis, University of Auckland $116,805 - W& BMiller Scholarship Synucleinopathies are a devastating group of neurodegenerative disorders defined by the abnormal accumulation of α -synuclein protein within the brain. This α -synuclein build-up subsequently leads to the progressive degeneration of neuronal and non-neuronal brain cell types. Despite being defined by this common pathological event, synucleinopathies exhibit extensive variability in their specific pathologies, progression and clinical dysfunctions. It was recently discovered that α -synuclein can adopt different structural forms (strains) that impart strain-specific functional properties. In this project JamesWiseman aims to identify and characterise these α -synuclein strains within the human brain and investigate how they affect different regions and cell types across α -synucleinopathies. PhilipWrightson Fellowship Tetrahydrobiopterin supplementation as a therapeutic approach to treat motor neuron disease Dr Angus Lindsay Mentor: Prof Aaron Russell, Deakin University $317,820 Motor neuron disease (MND) is a fatal neurodegenerative disorder. Death occurs from skeletal muscle wasting and paralysis. The vasculature, which delivers oxygen and essential nutrients to the body, is compromised in MND. A compromised vasculature can induce skeletal muscle wasting and accelerate disease progression. Tetrahydrobiopterin (BH4), an essential compound necessary for many biological reactions, regulates vascular health and function. Notably, synthesis of BH4 is impaired in MND. This project will understand how BH4 regulates MND progression through vascular function and test the therapeutic potential of BH4 supplementation for MND. The results could redefine future treatment strategies for MND. First Fellowship An in vitro organoid model of spinal cord injury to accelerate the translation of basic science to successful clinical outcomes Dr Brad Raos Mentor: Assoc Prof Darren Svirskis, University of Auckland $229,185 Spinal cord injury is a devastating condition that significantly compromises quality of life. There are few treatment options available for injured patients and the body’s natural healing mechanisms are generally not enough to provide meaningful recovery. To enable testing of a large number of new treatments there is a critical need for non-animal models that closely replicate human spinal cord injury. This project addresses that unmet need by using human stem cells to grow ‘mini-brains’ that form structures similar to the human spinal cord. The model spinal cords can then be damaged and used to test how new treatments promote healing. VJ Chapman Fellowship Prevalence and carrier rates of genetic mutations associated with mitochondrial disease in a healthy cohort and genotype:phenotype correlations Dr EloiseWatson Mentor: Prof Carolyn Sue, Royal North Shore Hospital and Kolling Institute of Medical Research, New SouthWales $36,000 Mitochondrial disorders, collectively the most common group of inherited metabolic disorders, may present with a wide spectrum of clinical manifestations at any age, frequently involve the neurological system, and may cause multisystem dysfunction. Despite their collective burden, potential for treatment and implications for affected individuals and their families, accurate estimates of the frequency of genetic mutations associated with mitochondrial disease (MD) and their spectrum of manifestations in the community is limited. Dr EloiseWatson seeks to determine the prevalence of MD genetic mutations through examining a large, healthy, community cohort, and to evaluate their impact on affected persons. Senior Research Fellowships Investigating inflammation-induced synapse loss using adult human neurons Dr Kevin Lee Mentors: Assoc Prof Johanna Montgomery, Prof Mike Dragunow, University of Auckland $202,036 We believe that human brain disorders are best studied using human brain tissue. With the recent establishment of a research platform that enables maintenance of adult human brain slices in a dish, Dr Kevin Lee seeks to identify and validate a human-specific pathogenic mechanism that underlies neuroinflammation, a major pathogenic contributor to many neurodegenerative diseases. Dr Lee’s goal is to use these living human brain cells to further our knowledge of the human brain and its pathology, and screen potential pharmaceutical drugs that can be used as treatments for people diagnosed with neuroinflammation-related disorders. Headlines 17