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12 Headlines Grant round – 2022A New studies into dementia, DNA, Batten disease, Duchenne muscular dystrophy (DMD), and obesity and the brain are just some of the incredible research projects to receive grants from the Neurological Foundation in our latest funding round. A mong the awards were three fellowships, which are given to early-career researchers to help establish themselves in their chosen fields. There were also five project grants, the main avenue by which the Foundation sponsors research, and five small project grants to encourage clinicians and scientists to undertake small- scale or pilot studies that may lead to a larger project. In addition, the Foundation granted five travel and two conference and training grants. In total, $1.6m was granted to potentially life-changing research, and to support the development of outstanding medical professionals with an interest in neurology. Congratulations to all of the scientists and clinicians who were successful in this round. Project Grants Dr Ashleigh Barrett-Young, University of Otago Investigating a blood-based biomarker of Alzheimer's disease in a longitudinal birth cohort $217,419 A blood test for early Alzheimer's disease is getting closer to reality. In this project, we will investigate a promising blood biomarker of Alzheimer's disease, pTau181, in members of the Dunedin Study. Aged 45 when their blood was collected, this project will tell us a lot about the processes of Alzheimer's disease in its earliest stages, and may help to identify people who are at risk of developing Alzheimer's while they are still middle-aged and when lifestyle and pharmacological treatments may be most effective. Professor Julia Horsfield, University of Otago How does cohesin insufficiency alter brain development? $239,953 Every neuron contains two metres of DNA packaged into a tight space: the nucleus. Interestingly, the activity of a neuron can change how DNA is packaged! And vice versa, the DNA ‘wiring’ of the nucleus appears to be important for how neurons function. We work on a protein, called cohesin, that is responsible for DNA packaging in the nucleus. We already know that genes don’t work normally when cohesin is reduced in the brain, and in this project, we will find out how reduced cohesin affects neuron activity and brain development. Humans with cohesin insufficiency experience a spectrum of neurological disorders including autism, and we hope our work will increase understanding and improve management of neurological conditions. Dr Owen Jones, University of Otago Aberrant calcium channel signalling in a model of frontotemporal dementia $208,276 Frontotemporal dementia is a severe neurodegenerative condition that currently has no cure. This form of dementia is often caused by genetic mutations that trigger a toxic accumulation of the protein “tau”. We have recently found that calcium channels on nerve cells are aberrantly engaged in one model of frontotemporal dementia with a tau-based mutation. We will investigate the link between tau and calcium channels, and probe the knock-on effects of calcium channel activation in our existing model and in a second model harbouring a different genetic mutation. We will also test whether calcium channel blockers can reinstate regular nerve cell function in these models. Dr Nadia Mitchell, Lincoln University Investigation of spinal cord pathology in sheep with CLN5 and CLN6 Batten disease $80,610 Batten disease (neuronal ceroid lipofuscinoses, NCL) are rare fatal inherited neurodegenerative diseases. Presently there is no cure, but brain-directed gene therapies look promising. Due to the profound impact of neurodegeneration, pathology outside of the brain is often overlooked but recent studies in NCL mouse models suggest the disease may start in the spinal cord. This study will examine whether spinal cord pathology also occurs in two naturally-occurring sheep models of NCL and if it precedes brain pathology. This will inform on optimal delivery routes for NCL gene therapies, particularly if they should target both the brain and spinal cord.