Studying Molecular Aspects and Contributions of Microglia in Brain Context

Microglia are resident brain macrophages that seed the CNS before birth and subsequently maintain themselves behind the blood brain barrier through longevity and limited self-renewal. Given their seclusion, the study of microglia in their physiological context has long been compromised by the absence of suitable experimental systems. We recently developed a novel inducible Cre recombinase-based approach that allows us to specifically genetically manipulate microglia in otherwise intact animals. Here we propose to use the respective CX3CR1CreER mice to investigate the role of microglia-derived membrane-bound and shed TNFα to the maintenance of brain homeostasis, as well as the development of autoimmune inflammation and de- and remyelination. In a second line of experiments we aim to perform a detailed characterization of the phenotypic changes microglia undergoes in comparison to infiltrating monocyte-derived macrophages in neuroinflammation. Moreover we will combine the CX3CR1CreER transgene with a RiboTag transgene to perform a gene expression profiling of microglia in health and disease.

DFG-Verfahren Forschungsgruppen

Teilprojekt zu FOR 1336:  Von Monozyten bis zu Hirnmakrophagen -Einflüsse auf die Eigenschaften myeloider Zellen im Gehirn

Internationaler Bezug Israel