Prion diseases are cause by prions, which are mis-shapen forms of a normal protein in the body that become infectious and toxic to cells. Prion diseases are often difficult to diagnose because they show a wide variety of different symptoms and variable times from illness onset to death. It is thought that these variations could be due to small changes in the shape of the prions, which allows them to selectively attack some brain cells more than others. Recently we developed a new prion disease model by reprograming skin cells in the lab into small spheres of living human brain cells called cerebral organoids. New developments in organoid technology permit ‘tweaking’ of the cells in the cerebral organoid to be more like those found in different parts of the brain (i.e. the front of the brain versus the back). Using brain cells that mimic different parts of the brain, we can look at how prions attack different human brain cells and determine which cells are most vulnerable.

In this study we will combine the new human prion disease model with another relatively new technique called single-cell sequencing. The single-cell sequencing technique allows us to look at the changes occurring in every single cell in the organoid following infection with human prions. This will show us which brain cells are most affected by prion infection and what changes are happening inside them. With this information, we hope to learn what causes certain cells to be more vulnerable to infection and how we might in the future protect them from the attacking prions.