Nuclear mechanical collapse of Purkinje neurons in Ataxia-telangiectasia
In-person only
Ataxia-telangiectasia (A-T) is a neurodegenerative disorder caused by ATM mutations, leading to progressive Purkinje neuron loss. While ATM regulates the DNA damage response, mechanisms of cell degeneration remain unclear. Using cerebella, hiPS cells, and cerebellar organoids from A-T patients, we show that Purkinje cells shift from a soft, low-viscosity state to hyperstiffness with nuclear deformation and chromatin hypermethylation. Proteomics reveal dysregulated mechanotransduction, chromatin remodelling, and loss of calcium channels. Epigenetic inhibition restores nuclear structure and ITPR1 levels. These findings identify A-T as a “mechano-disease” and suggest that targeting nuclear mechanics could offer new therapeutic avenues
Date:
23 July 2025, 12:00
Venue:
Kennedy Institute of Rheumatology, Headington OX3 7FY
Venue Details:
Kennedy Lecture Theatre
Speaker:
Dr Conor Lowndes (FIRC Institute of Molecular Oncology)
Organising department:
Kennedy Institute of Rheumatology
Organiser:
Magdalena Gross
Host:
Professor Mike Dustin (Kennedy Institute of Rheumatology)
Part of:
Kennedy Institute Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Katie Roberts
