Genetic studies have revealed many inherited risk factors for complex diseases, but turning these discoveries into therapies requires understanding how genetic variation changes cell function. This project aims to uncover how genetic variation affects microglial cells—the brain's immune cells that respond to harmful protein aggregates such as amyloid-ß and tau found in Alzheimer's disease. Using advanced single-cell and spatial genomics, we will define how microglial states emerge in response to neurodegenerative disease-related stressors and how these states manifest within diseased brain tissue. We will also apply deep learning to predict how genetic risk variants alter acquisition of these states. Together, these approaches will reveal relations between genetics and microglial behaviour and its contribution to neurodegenerative diseases such as Alzheimer's disease, providing new directions for therapy development.

2026

2030