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14 Headlines Dr Indranil Basak grows brain cells in a lab before infecting them with strains of a deadly virus that has spread around the globe. It sounds like the stuff of science fiction, but this type of leading-edge research taking place in New Zealand is vital in helping us understand the long-term impacts of COVID-19. Dr Basak is part of the NeuroCOVID-19 research team at the University of Otago in the Hughes Lab, along with Dr Lucia Schweitzer, Jennifer Palmer, with guidance from neuroscientist Associate Professor Stephanie Hughes, and virologists Professor Miguel Quinones-Mateu and Dr Rhodri Harfoot. Before COVID-19, the research team based at the Brain Health Research Centre developed a breakthrough method to grow brain cell cultures, or neurons, in a lab using stem cell technology. With funding from the Neurological Foundation, Dr Basak used the cell technology to better understand Batten disease, a fatal condition of the nervous system that typically affects children. When the pandemic emerged it became apparent that the lab’s methods could also be a vital tool in understanding the virus’ neurological impacts. Results from the Otago NeuroCOVID-19 study will hopefully lead to answers related to long-term symptoms, many of which are presenting as neurological. The NeuroCOVID-19 study began in mid-2020, when the virus had infected some 16 million people worldwide. Today, case numbers have skyrocketed to 180 million cases and over 3.8 million deaths (at time of print), with the real case numbers expected to be much higher. This presents some frightening scenarios given the emergence of long-term symptoms among those that have recovered, months after the human body has cleared the virus. “By the end of 2020, it was apparent that some COVID-19 patients were displaying neurological symptoms ranging from dizziness, disturbed consciousness, headache, loss of smell and taste, seizures, encephalitis, to an increased risk of stroke. Furthermore, a small percentage of patients also developed symptoms usually associated with Parkinson’s disease,” Dr Basak says. Some of the lab’s early findings have revealed the rate of infection is greatest in the mature neurons (see image) compared to the precursor and immature neurons and was enough to kill these neurons. “How the virus alters neurological processes giving rise to neurological symptoms is still unclear. It is known that the virus can cross the blood- brain barrier, as evident from the post-mortem reports from several COVID-19 patients. Whether dying infected neurons have a secondary effect on neighbouring neurons, leading to neurological symptoms, is a possible explanation,” Dr Basak says. This theory will be tested as part of the research and will help identify where to target drugs to treat neurological symptoms. The project has been funded by the University of Otago Brain Health Research Centre, Brain Research New Zealand, and Otago Medical Research Foundation. Dr Indranil Basak is a research fellow in the Department of Biochemistry at the University of Otago in Dunedin. He studies genetics and neurodegenerative diseases like Parkinson’s disease and Batten disease. Dr Basak is originally from India and began his journey in science when he travelled to the United Kingdom for his Masters in Science. He did his PhD in Biological Sciences at St. John's University, New York, focusing on neurodegeneration in Parkinson's disease. After his PhD, Dr Basak moved to Utah for his first postdoctoral training in haematology. Following his passion to learn more about the human brain and to reunite with his partner in New Zealand, Dr Basak started his postdoctoral research in Associate Professor Stephanie Hughes’ group in Dunedin. His research aim is to understand the underlying mechanisms involved in neurodegeneration in Parkinson’s disease and Batten disease and continue learning more about the human brain. More recently he has been part of a team investigating the neurological impacts of COVID-19. NeuroCOVID-19: new discoveries being made in NZ

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