UK DRI Seminar: Dr Kathryn Bowles

Hosts: Francesca Lam and Marc Aurel Busche

Abstract: 

"Despite most closely resembling foetal brain, iPSC-organoid models have repeatedly demonstrated an ability to recapitulate key cellular phenotypes associated with neurodegenerative diseases. While there are still concerns in the field regarding their reliability, consistency and relevance to adult-onset diseases, methodological and technical modifications are constantly improving organoid models. As such, they are proving to be incredibly valuable for understanding the early stages of cellular dysfunction that occur prior to the onset of disease and subsequent neuronal death. We use iPSC and organoid models to study primary tauopathies, such as frontotemporal dementia and progressive supranuclear palsy, caused by mutations in the MAPT gene. We have found that while different MAPT mutations have unique functional effects, they converge on similar functional consequences. In particular, we observe early synaptic dysfunction that causes neuronal hyperactivity, which renders MAPT mutation neurons to be more susceptible to excitotoxicity and cellular stress. We are now developing new tools and assays to study these mechanisms in more detail in our organoid systems, with the goal of better understanding early, prodromal stages of disease. "

If anyone would like to speak with Kathryn on the day, they can email Francesca Lam francesca.lam.19@ucl.ac.uk.