Determining molecular mechanisms linking SARS-CoV-2 infection to neuronal developmental defects and neurodegenerative disease

• Applicant: Dr. Romano Strobelt
• Subject Area: Virology ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550670861

Over 30% of hospitalized COVID-19 patients show neurological symptoms, like loss of taste or smell, nausea, headaches, and cognitive dysfunction, which can develop into long-term manifestations. SARS-CoV-2 has the potential to infect neuronal cells in patients and different kind of brain cells in culture, including neurons. Histopathological signs of brain damage are found in 25% of individuals who died of COVID-19. However, it is unclear how this virus induces immunologic responses to infection in the brain or the consequence on neural development and functionality. To gain further insights into the neuropathological and neurological consequences of COVID-19 and possible cellular and molecular mechanisms, we will investigate the functionality of SARS-CoV-2 and SARS-CoV-2 proteins in neurons using state-of-the-art proteomics approaches. To this end, we will generate induced neurons (iNeurons) from human fibroblasts, which preserve age-associated hallmarks, and introduce them to SARS-CoV-2 or respective isolated proteins followed by proteomics and data-integrative analysis to identify key proteins and processes with potential involvement in neurogenesis as well as neurological diseases. These studies will help us understand the basic principles of how SARS-CoV-2 impacts biological processes in neuronal cells and how virus-induced cytokines contribute to the development of SARS-CoV-2-related neurological diseases.

• DFG Programme: WBP Position