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Meet DR BLAKE HIGHET The Neurological Foundation Human Brain Bank Research Fellow Dr Blake Highet is awestruck every time he handles a precious donation of brain tissue. Last year, he was appointed the Neurological Foundation (NF) Human Brain Bank Research Fellow at the University of Auckland’s Centre for Brain Research – a dream role for any aspiring neuroscientist. H is role is unique. Blake is adopting cutting-edge techniques to preserve post-mortem brain tissue. It’s a chance to apply his deep understanding of the brain’s molecular mechanisms, gained during his two-year, Neurological Foundation-funded Philip Wrightson Fellowship at the University of Utah. Already, he has made strides in improving how the NF Human Brain Bank can use tissue for more advanced research techniques than previously possible. As custodians of tissue from more than 1000 brains, Blake is also looking at ways to prolong the quality of existing tissue. “Some of the samples in the brain bank date back 30 years,” he explains. “The tissue is preserved in formalin. It’s a common but harsh preservative that we still use today. However, eventually it diminishes the tissue’s molecular integrity. “So I’m asking, ‘When fresh tissues come in, are there gentler alternatives that could preserve the sample quality for future research?’ and ‘What else can we do with the tissue we already have?’ “Getting the most from brain tissue is useful for our research, but is also incredibly meaningful to the families we work with.” New techniques are changing the way brain tissue is studied. Spatial transcriptomics and in-situ hybridisation methods are at the cutting edge. In the simplest terms, they give a more comprehensive picture of the behaviour of genes and cells in the brain. Retaining RNA quality is essential as these techniques advance, so Blake is trialling other fixation methods, such as methanol-based preservatives, that might retain better RNA quality in archived tissue, making for more meaningful samples years down the track. “We have techniques now like whole-transcriptome coverage, where we can look at every gene in the entire genome on a single piece of tissue – but it relies on the quality of the tissue.” Blake says he is fortunate to work alongside NF Human Brain Bank Co-Director Professor Maurice Curtis – who originally inspired him to study the brain. Maurice’s first year lecture on neurogenesis – the brain’s extraordinary ability to grow new neurons – was Blake’s ‘aha’ moment. He switched his goal from becoming a medical doctor to being a neuroscientist. “When you're young, and you do something like knock your head, you’re told you’ve ‘killed brain cells’. But Maurice went against that mantra, and that drew me in.” Blake went on to complete Honours and PhD degrees under Maurice’s supervision, before being awarded the Neurological Foundation Philip Wrightson Fellowship. The prestigious fellowship is designed to give emerging neuroscientists skills at a top international research institute, before returning that knowledge to New Zealand. In Utah, Blake worked in the memory lab of Dr Jason Shepherd, a world-leading Professor of Neurobiology, on a research project looking at molecular contributors to memory loss in Alzheimer’s disease. While Blake gained vital lab skills in the United States, it also made him realise how well New Zealand does brain research. “One of the things I really missed was the connections we have in New Zealand with patients and the community,” he says, adding that people may not realise how involved the Centre for Brain Research at the University of Auckland is with people with neurological disease, making its research especially meaningful. “Much of what researchers uncover in labs can feel distant from patient realities, especially in the specialised field of neurodegeneration,” Blake says. “I don’t want to lock myself away in a lab because it becomes very easy to forget the reason we are doing all of this. It’s the patients and their families.” Headlines 11