New technologies for target discovery in neuropsychiatric disorders

The project officially started in October 2022 and the efforts have since been divided into five work packages (WPs), as originally described in the project description. Progress report as of September 2024: Project administration (work package, WP5): After the official project kick-off meeting on October 24, 2022, all WP leaders and other project participants have gathered for regular project meetings at 2 month intervals and weekly targeted project meetings. Hiring of the first postdoctor and the PhD candidate was on time and hiring of the second postdoc was slightly delayed. As the second and third postdocs left for permanent positions outside the university, these positions have been advertised again, resulting in almost one year delay of their tasks. Except for these delays, the project is well underway and progressing according to plans. In WP1 we are developing a pipeline using machine learning for extracting possible molecular treatment targets using multi-omics data. In WP2 we are exploring promising treatment targets using in silico and in vitro biochemical methods and structural biology. In WP3 and WP4 we are optimizing drug leads and testing these on purified proteins and in mammalian cell cultures. So far, none of the new compounds have been tested in animal models (WP4).This work will be prioritized towards the end of the project period.

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.