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INTPART-International Partnerships for Excellent Education and Research

Simulating the multi-scale pathophysiology of mental illness

Alternative title: Simulering av multi-skala patofysiologi av psykisk sykdom

Awarded: NOK 3.0 mill.

SIMENT seeks to enhance partnerships between leading scientists in Norway and California who are together developing approaches for understanding the genetic basis of mental illness. Methods for defining the genes and gene modifications that predispose individuals to developing mental illness are developing rapidly, and the members of SIMENT are at the forefront of this progress. With these advances in genetic mapping comes a tremendous amount of information that is surely of great value for developing new and effective treatments. However, a key step for translating genetic information into rational treatments for patients, is understanding how modifications to gene function manifest as the complex neuropsychological processes that underlie mental pathology. The core principle of SIMENT is that a key requirement for this understanding, and developing rational treatments, is a set of mathematical and computational tools for assessing the effects of genetic variation on the physiology of the brain. To address this need, SIMENT combines world-leading expertise in clinical psychology, experimental and computational neuroscience, systems biology, and mathematics to generate new mathematical and computational tools for these purposes. We provide opportunities for young scientists and senior researchers at the University of Oslo (UiO), University of California, San Diego (UCSD), and Simula Research Laboratory (Simula) to interact frequently and in a way that is specific to the research problems they are working together to solve. SIMENT will also provide fully-funded opportunities for neurobiologists in a summer school in computational physiology conducted between Simula and UCSD from 2019-2023. This school covers material central to SIMENT, and exposes Norwegian students to world-leading international researchers in a strongly multidisciplinary environment. Tools developed by the groups will be shared, showcased, and demonstrated through the school.

The SIMENT project has resulted in 71 publications over the funding period, representing a strengthening collaborative relationship between Simula, UiO and the University of California San Diego in the field of computational neuroscience. Many of the papers have been published in high impact journals such as Nature Neuroscience, The American Journal of Psychiatry, eLife, Translational Psychiatry, and JAMA Psychiatry, among others. The focus of the research performed was on developing computational and biophysical approaches that can bridge the gap between bioinformatics and clinical outcomes in a variety of conditions such as schizophrenia and Alzheimer's disease. For example, novel bioinformatics tools were developed and Genome Wide Association Studies were employed to identify overlapping genetic loci between a variety of conditions: Parkinson's Disease and schizophrenia, psychiatric disorders and sleep disorders, bipolar disorder and risk-taking behaviour, and mood instability and alcohol use disorder, to name a few. These advances in understanding of genetic underpinnings for psychiatric conditions allow for greater understanding of brain function, and uncover potential therapeutic pathways. SIMENT funding allowed for enhanced collaboration between bioinformatics, modeling, and experimental science cores at partner institutions. SIMENT supported a number of short- and long-term research visits for PhD students, post-doctoral scholars, and senior scientists. This has allowed for faster publication and dissemination of scientific results, as well as close inter-institutional collaboration that will continue beyond the project period. A portion of SIMENT funding was used to support the Simula Summer School in Computational Physiology. This summer school is a world class training mechanism for graduate students in computational physiology, which is focused on multiscale modeling of excitable tissues. During the project period, 124 students were trained through four editions of the summer school, which took place annually with the exception of 2020, when the school was cancelled due to public health concerns. Two anthologies of student reports have been published as SpringerBriefs during the project period, which demonstrate the high caliber of project work during the school.

This project is focused on multidisciplinary neuroscience and aims to leverage existing and overlapping collaborations between top academic researchers at the University California, San Diego, the University of Oslo, and Simula Research Laboratory. In particular, the following expertise will be shared and expanded through this project: clinical expertise in mental illness (NORMENT/UiO), computational and experimental neuroscience (CINPLA/UiO), mathematical modelling of excitable tissues (SIMULA), analytical and engineering expertise (CTIPM & NIL/UCSD), and multi-scale computational modelling (CMRG/UCSD). Students and investigators will benefit and learn from the particular expertise of one another, accelerating the development of world-class research and education in Norway in this complex and competitive field.

Funding scheme:

INTPART-International Partnerships for Excellent Education and Research