Adriano Aguzzi, MD and Vangelis Bouris, MSc

Grant Title: Investigating the role of BLOC-1 complex in prion disease

Location: Institute for the Science of the Aging Brain (ISAB), St. Gallen, Switzerland

Grant Year: 2026

Creutzfeldt-Jakob disease (CJD) is caused by misfolded proteins called prions that spread from one cell to the next, leading to severe brain damage over time. A promising way to slow or stop the disease is to block prion spread from cell to cell. We discovered that BLOC-1 (Biogenesis of lysosome-related organelles complex 1), a group of proteins inside cells, is essential for prions to move between cells. Importantly, we found that reducing BLOC-1 levels blocks prion infection in human cells grown in the lab, but the mechanism of how this happens remains unclear. BLOC-1 is part of the cell’s ‘shipping’ system, responsible for the transfer and recycling of proteins inside the cells. However, the function of BLOC-1 is unclear and it has never been linked to prions or other neurodegenerative diseases. In this project, we propose to identify how BLOC-1 helps prions spread and test whether lowering BLOC-1 levels would stop prion infection in disease-relevant models such as prion-infected mice. Understanding this pathway may ultimately point to new therapeutic strategies to combat CJD.

About the Researchers:

Dr. Adriano Aguzzi
Adriano Aguzzi has devoted his professional life to deciphering the role of the immune system in prion diseases. The importance of his work is acknowledged by more than 80’000 citations (H-index: 143). Aguzzi’s findings of pervasive colonization of the immune system by prions convinced governments worldwide to undertake efforts to limit human exposure to prions derived from farm animals. His finding of the B-cell requirement for prion spread was the basis of the UK’s decision to introduce universal leukodepletion of blood donation – a measure that may have saved many human lives. His work demonstrated that chronic inflammation controls the organ tropism of prion diseases, thereby clarifying how scrapie prions propagate horizontally within sheep flocks. His discoveries were
shown to be valid for all common neurodegenerative diseases including Alzheimer’s (AD) and Parkinson’s.

Dr. Vangelis Bouris
Vangelis Bouris is a PhD candidate in the Molecular Life Sciences PhD Program at the University of Zurich. He holds an MSc in Cellular & Molecular Neuroscience from the University of Tübingen. In his doctoral research under the supervision of Prof. Adriano Aguzzi, he applies genome-wide genetic screens to identify the molecular pathways that drive prion propagation.