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TRR 274:  Checkpoints of Central Nervous System Recovery

Subject Area Medicine
Biology
Term since 2020
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 408885537
 
In most organs, tissue damage is a reversible process that is followed by an efficient regenerative response that re-establishes tissue structure and function. In the mammalian central nervous system (CNS), however, injuries often result in persistent lesions that permanently alter tissue function and sometimes even result in progressive neurological deficits. Despite the CNS’ poor tolerance to damage and its low regenerative capacity, the response to acute CNS injury can be variable and ranges from irreversible damage to almost complete recovery. The underlying reasons for these different outcomes are unknown. A central obstacle for progress in this area has been the complex biology underlying the response to CNS injury which, irrespective of its trigger, is followed by a multicellular response that encompasses different cell types (including neurons, astrocytes, microglia, oligodendrocytes, and their precursors, as well as infiltrating immune cells). Therefore, the major aim of this CRC is to understand the biology of the multicellular response that determines recovery after CNS injury and to identify the checkpoints that govern the balance between perpetuation of tissue damage and restitution of function. We explore the unique patterns of damage and reconstitution resulting from various acute insults to the CNS caused by inflammation, trauma, metabolic dysfunction, or ischemia and seek to unravel the underlying mechanisms that dictate whether the tissue undergoes a regenerative or scarring response. Our CRC consists of immunologists, neurobiologists, and glial biologists, specialized in intra-vital, cell-biological, and molecular analyses of acute CNS damage. These complementary expertises and approaches allow us to reveal and modulate cellular interactions and their structural and functional consequences as well as their underlying molecular signals and pathways. Our goal is to define the immunological, glial, and neuronal checkpoints that determine the outcome of CNS injuries, and to develop intervention strategies targeting those checkpoints that guide an injured CNS tissue towards reconstitution. In the first funding period our focus has been on the analysis of distinct damage models and the cellular responses, subcellular alterations, and molecular signals that determine recovery. In the second funding period we want to build on these insights and emphasize approaches that allow i) dissecting the cellular networks and interactions that interconnect immune, glial and neuronal responses after injury, ii) integrating findings across distinct injury models to reveal shared and disease-specific principles of the recovery process and iii) validating experimental findings in human tissue samples and humanized model systems. Together, these studies will lay the foundation for the design of novel treatment strategies that harness the endogenous repair potential of the CNS to promote tissue restitution and limit scarring.
DFG Programme CRC/Transregios

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Applicant Institution Georg-August-Universität Göttingen, since 1/2024
Spokespersons Professor Dr. Alexander Flügel, since 1/2024; Professor Dr. Mikael Jakob Simons, until 12/2023
 
 

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