Project Details
Projekt
The role of translation in shaping microglial activation states during neuroinflammation
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 559329136
Proper regulation of microglial activation, governed by the balance between activation and return to an inactive state, is critical for maintaining homeostasis and brain health. Disruption of this balance contributes to the pathology of numerous brain disorders. We have recently discovered that the formation of stress granules containing TDP-43 shifts this balance toward chronic microglial activation and prolonged neuroinflammation following traumatic brain injury. Notably, protein translation is altered in these stress granule-containing, persistently activated microglia. In this collaborative project, we will leverage the complementary expertise of the Kiebler Lab in protein synthesis and the Ninkovic Lab in neuroinflammation to address several key objectives: 1. How changes in protein translation influence microglial activation (Work Package 1). 2. Identify proteins with altered translation that are relevant for regulating the microglial activation (Work Package 2). 3. Unravel the mechanisms leading to altered protein translation in activated microglia (Work Package 3). 4. Identify specific functions of activated microglia that are modified in a protein synthesis-dependent manner (Work Package 4). By uncovering the regulation of translation and identifying previously unrecognized translation-dependent mechanisms that control microglial reactivity, we aim to reveal novel regulatory principles that drive microglial activation and influence neuroinflammation. These insights will pave the way for innovative strategies to reverse disease-associated microglial states, restoring them to their healthy, physiological functions.
DFG Programme
Priority Programmes
