Defense of Mathilde Colinet's thesis

Today, the first Ph.D student from the ADMG Team, Mathilde Colinet, successfully defended her Ph.D entitled: "3D human cortical brain organoids derived from human PSC to model the human brain in health and disease".

Big congratulations to Mathilde Colinet for this achievement!

Mathilde Colinet's LinkedIn profile

Abstract 

3D human cortical brain organoids derived from human PSC to model the human brain in health and disease

This thesis investigates human brain development and diseases related to adulthood using brain organoids to overcome the limitation to the access of human brain tissue. First, we studied the healthy development of the human brain. We demonstrated a time-dependent emergence of neuronal and glia populations in our model alongside with an increase in calcium activity and changes in axonal transport related to maturation. Then, we investigated the impact of SARS-CoV2 infection on brain organoids and identified astrocytes as the major cell type infected. This infection triggers a global mild inflammation and upregulates the expression of astrogliosis markers. However, no cell death was detected, rather an upregulation of markers promoting cell survival was observed. Finally, we focused on the study of the development of Alzheimer’s disease using cell lines derived from patients. The characterization of our model revealed an early stage of the disease associated with neuronal hyperexcitability. We also showed lower levels of cathepsin D in lysosomes independent from amyloid beta peptide levels. Overall, this thesis showed that brain organoids are powerful models to understand the development and functionality of our human brain but also to decipher the mechanisms of viral infection and neurodegenerative diseases such Alzheimer’s disease.