Research Johanna Van den Daele

Abstract

Defects in the microtubule associated protein tau typify a range of neurodegenerative disorders termed tauopathies, which includes Alzheimer's disease. Recent studies point to the potential involvement of cellular senescence, an irreversible non-proliferative state, associated with inflammatory cytokine secretion, in disease development. However, the causality, timing, and afflicted cell types remain poorly characterized. The goal of this project is to define the exact causal relationship between senescence and tauopathy development in a human context. To achieve this, I intend to produce human iPSC-derived brain organoids that contain the three major cell types of the brain (neurons, astrocytes, or microglia) and assess the emergence of senescence therein using deep coverage microscopy and single cell sequencing. Once a cell-specific senescence signature has been established, I will measure its penetrance in mutant organoids that recapitulate the hallmarks of tau pathology. Finally, I will evaluate whether senescence-targeting compounds modulate tau pathology and influence organoid condition. Together, this work should allow defining whether senescence is a driving factor in human tau pathology development and unveil its potential as druggable node.

Researcher(s)

• Promoter: De Vos Winnok
• Co-promoter: Ponsaerts Peter
• Fellow: Van den Daele Johanna

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project