Finding cures for the future in the brains of the past

For decades the microscopic study of brain tissue has helped pathologists understand disease, describe the cellular diversity of the nervous system and define specific features of brain disorders. In parallel, neuroimaging methods have revealed the function and dysfunctions of whole brain neural circuits. However, technical limitations of traditional microscopy have made it difficult to relate cellular level advances to whole brain observations.

Our approach unifies neuroscience across scales, from genes to the whole brain, with the goal of revealing the mechanisms of brain disease, establishing diagnostic biomarkers and identifying new therapeutic targets. 

The collaboration

This collaborative project with the University of Geneva (UNIGE) and Hôpitaux Universitaires de Genève (HUG) takes advantage of the Geneva Brain Collection (GBC) as well as healthy and diseased human brain tissue from other sources. 

The GBC is one of the largest brain collections in Europe, containing more than 10,000 post-mortem human brains. The GBC has collected brain samples and associated medical records since the beginning of the 20th century, and so offers an exceptional opportunity to gain new insights into the fundamental basis of brain disease.

Advances in imaging techniques, particularly lightsheet microscopy present at the Advanced Lightsheet Imaging Center (ALICe), enable the imaging of much larger samples while retaining their structure. 

The team will develop a next-generation histopathology approach taking advantage of novel molecular labelling techniques coupled with advanced microscopy and data analysis tools, to explore the relationship between cellular and whole brain mechanisms in both healthy and diseased tissue. It will initially focus on neurodegenerative dementia and eventually explore the broad range of conditions contained in the GBC.