The question of what makes each individual unique has fascinated neuroscientists for centuries. Of particular clinical relevance, different individuals, and even different cells within the same individual, can respond differently to the same disease-causing alteration or drug treatment. Mechanisms underlying such inter- and intra- individual variation are not well understood and are therefore the focus of this project. We hypothesize that some developmental and degenerative brain diseases increase cell-to-cell differences in a stochastic manner, which contributes to diverse outcomes. Leveraging single-cell analyses and CRISPR screening approaches in human brain cell types, we will explore mechanisms and modulators of variability. Ultimately, this work will help us to better understand basic biological principles and support the development of more precise treatment strategies for brain diseases.