The cytoskeleton as a signaling node that contributes to microglia activation and diversity

Microglia change their morphology under inflammatory conditions by cytoskeletal changes.
We recently found evidence for a reverse relationship between inflammation and cytoskeletal changes: A targeted deletion of a cytoskeleton-regulatory factor in microglia not only lead to changes in microglial morphology but also to a pronounced microglial inflammatory state.
Microglial genes encoding for different actin cytoskeleton-regulatory factors have been implicated as risk genes in Alzheimer’s disease and neurodevelopmental diseases such as autism and schizophrenia. This suggests that the cytoskeleton may contribute to microglial effector functions in neurological disease.

Thus, in this project we aim to study how actin cytoskeleton pathways modulate microglial activation, and identify involved innate immune pathways and cellular mechanisms. Furthermore, we will characterize the role of microglial cytoskeleton-regulatory factors in CNS and synapse integrity under physiological condition and upon maternal immune activation (MIA) in vivo.
We plan to employ state-of-the-art experimental methods including conditional mouse models, 3D microglia cultures, human post-mortem CNS tissue, optogenetic modulation of the cytoskeleton and transcriptomic and epigenetic profiling.