Investigating microglial interactions driving neurodegeneration in PD

Next to the well-characterised loss of dopaminergic neurons in Parkinson’s disease, the support cells of the brain, the microglia and astrocytes, are also changed in the disease. From other diseases, such as Alzheimer’s disease, it is known that microglia play a very important role in communicating with neighbouring cells (Mallach et al., 2024), which can drive a toxic cascade leading to cell death. Less is known about the role of mciroglia in Parkinson’s disease, but risk genes linked to the disease, such as LRKK2, modify micorglia function, suggesting that microglia play an important role in disease initiation or progression.

Dr Anna Mallach's lab takes advantage of state-of-the-art techniques to understand microglial interactions with other cells in Parkinson’s disease and identify what changes in cellular interactions drive cell death. The aim is to understand how the disease and symptoms develop to be able to target them earlier and more efficiently. To understand the key components of this crosstalk, the team will use:

1. Functional readouts using induced pluripotent stem cells modeling human brain cells
2. Genetic pertubations working with known risk genes to assess how they disrupt cellular interactions
3. Molecular analysis of cellular interactions in patients using bioinformatic analysis of big datasets, such as publicly available RNA sequencing datasets