Thomas Misgeld

https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...

The Z01 Bioimaging and Tissue Analysis Platform supports various CRC projects by analyzing human tissue samples and using state-of-the-art correlative light and electron microscopy techniques to study CNS recovery at a detailed level. During the first funding period, Z01 contributed to understanding key aspects of CNS recovery, such as axon damage, inflammation’s role in tissue healing, and how certain cells help repair nerve fibers. In the next funding phase, our focus will be on two main goals: ...

In multiple sclerosis, an “energy crisis”, which entails axonal ATP depletion, contributes to neuronal dysfunction and ensuing neurodegeneration. We have identified dysregulation of the TCA cycle and specifically depletion of its pacemaker enzyme, IDH3, as a critical checkpoint of neuronal energy homeostasis. Targeting IDH3, however, leads only to partial reversal of axonal ATP deficits, pointing to further neuroenergetic checkpoints. We now plan to identify these checkpoints and study their ...

In autoantibody-mediated gliopathies, such as Neuromyelitis Optica Spectrum Disorder, pathology often spreads quickly beyond the intital target cell type to affect other glial cells. In this project, we will identify glial-glia interactions that act either as checkpoints of acute pathology spread or as checkpoints of lesion repair. To achieve this, we will use in vivo imaging in animal models, as well as genetic interventions and close correlation with human neuropathology, to study how the ...