Project Details
Projekt
Actin cytoskeleton disturbance as a driver of cellular dysfunction and cell state diversity in microglia
Applicants
Professor Dr. Frank Bradke; Dr. Annett Halle
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Experimental Models for the Understanding of Nervous System Diseases
Immunology
Experimental Models for the Understanding of Nervous System Diseases
Immunology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 500299518
Microglia have highly ramified and motile cell branches. Many microglia functions depend on this high cell motility, including tissue surveillance and interaction with other CNS cells and synapses. Microglia adapt their cell shape in a controlled manner to perform these tasks. This in eukaryotic cells is regulated by the cytoskeleton. However, despite these facts, surprisingly little is known about the cytoskeleton in microglia. Some microglial actin cytoskeleton-regulating factors have been identified as risk genes for neurological disorders, suggesting an important role of microglia in disease pathology. In this project, we will therefore investigate how loss of one of these genes, CYFIP1, which has been genetically linked to autism and schizophrenia, contributes to cell dysfunction and a dual inflammatory response in microglia. By abolishing this inflammatory response using genetic mouse lines, we will delineate the impact of inflammation on microglial functions and cell state beyond the primary effect of cytoskeleton disruption. We will also investigate the role of the cytoskeleton in basic cell biological processes in microglia using 3D cell culture and human iPS cells. Lastly, since the expression of cytoskeleton-regulating genes is changed in microglia in neurodegenerative diseases, we will systematically investigate these changes in human postmortem tissue of patients with neurodegenerative diseases by performing multiplex in-situ hybridization analyses.
DFG Programme
Priority Programmes
