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TEKNOKONVERGENS-Teknologikonvergens - grensesprengende forskning og radikal innovasjon

New technologies for target discovery in neuropsychiatric disorders

Alternative title: Kombinasjon av molekylærgenetikk, strukturbiologi og maskinlæring for å avdekke nye behandlingsmål ved nevropsykiatriske lidelser

Awarded: NOK 20.0 mill.

Neuropsychiatric disorders include many conditions that affect the brain and that affect human behavior and health. This includes both common psychiatric diagnoses such as depression, developmental disorders and psychoses and neurodegenerative conditions that are often classified as neurological diseases. Such conditions are major causes of human suffering, loss of life and productivity worldwide. Drugs used against the diseases are often modestly effective, rather non-specific and were introduced 50-100 years ago, mainly based on accidental findings. Recent molecular genetic studies have identified clearly associated genetic markers and genes that are expressed in specific cell types in the brain. These studies have also pointed to proteins that may be therapeutic targets for future drugs. Major technological breakthroughs in the application of artificial intelligence to genetics and experimental molecular biology have been reported. The NeuroConvergence project will further develop, apply and combine these technologies. This requires coordinated efforts from specialists with different backgrounds. We have therefore established an interdisciplinary research group from two faculties at UiB with expertise in machine learning and biotechnology, including human genomics, protein structure biology, medicinal chemistry, pharmacology, and clinical neuropsychiatry. The project team will combine artificial intelligence, including machine learning, and advanced experimental biotechnology for the discovery and testing of new molecular treatment targets. These technologies are new and have never been combined for this purpose. Our ambition is to uncover radically new treatment goals. In parallel with the identification of new molecules, we will explore the medical relevance and therapeutic potential of enzymes involved in the production of neurotransmitters in the brain. These enzymes have already been found in ongoing pilot studies in our research group.

Neuropsychiatric disorders (NPDs) are major causes of human suffering, loss of lives and productivity all over the world. Currently used pharmacotherapies against NPDs have low efficacy and specificity and were introduced 50-100 years ago mainly based on accidental findings. However, recent molecular genetic studies have revealed strongly associated genetic loci, enriched in brain pathways and proteins, and possible new therapeutic targets for NPDs. Moreover, revolutionary new technological breakthroughs have been reported in computational and experimental molecular life sciences. These technologies will be refined, applied and combined in the NeuroConvergence project for systematic identification and testing of new molecular targets in the treatment of NPDs. The discovery of new treatment targets for disorders of the brain are inherently complex operations, depending on coordinated efforts by multiple partners from different backgrounds. For this purpose, we have assembled a core interdisciplinary research team from two faculties at University of Bergen, representing expertise in machine learning (ML) and biotechnology, including human genomics, protein structural biology, medicinal chemistry, molecular pharmacology and clinical neuropsychiatry. The project group will develop and apply artificial intelligence (AI) approaches including computation, modeling and simulation, ML, big data analyses and advanced experimental biotechnology to the discovery and testing of new molecular treatment targets. These technologies are new and have never been combined for this purpose. Our ambition is to reveal new and radically new treatment options. In parallel with the identification of new molecular targets, we will explore the druggability and treatment potential of recently identified targets identified in our pilot studies. The core group at University of Bergen will work closely with outstanding partner institutions in Germany, USA, Spain, and Sweden.

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TEKNOKONVERGENS-Teknologikonvergens - grensesprengende forskning og radikal innovasjon