DNA is the guardian of our genetic information, but it is subject to constant lesions, the most toxic of which are double strand breaks (DSBs). Defects in DNA repair lead to apoptosis, tumorigenesis, and cellular senescence, all cellular events that accompany aging as well as the progression of neurodegeneration in the brain. To understand the role of DNA damage fully, we propose to investigate why certain neurons may decline faster than others during the progression of aging and neurodegenerative disease using single cell data. In this thesis we build models of the damage status of single brain cells during neurodegeneration and show that they can be validated experimentally by imaging data, systematically assess methods for predicting age from single cell data, and lastly extend the Toolkit for Modelling Nested Trees to model the role of DNA damage in both neurodegeneration and aging. Understanding the cell type specific events downstream of damage is crucial both for therapeutic design and for linking molecular events to the neural circuits and the behaviors they are associated with.
Andreas Pfenning (Chair, CMU)
Maria Chikina (Pitt)
Seyoung Kim (CMU)
Karl Herrup (Pitt / Neurobiology)
Zoom Participation. See announcement.