Investigations

There is to date no therapy that prevents the devastating consequences of traumatic brain and spinal cord injuries. Previous work has shown that neuronal connections can spontaneously remodel after CNS injuries, a process that contributes to functional recovery. Here, we propose that the balance between adaptive and maladaptive neuronal remodeling depends on circuit refinement and is guided by the interplay between neuronal activity and microglia-driven synapse removal. We aim to identify the ...

This project focuses on recovery mechanisms of the CNS tissue in the course of acute T-cell mediated autoimmune inflammation. We hypothesize that T-cell induced changes of the grey matter are crucial for the failing recovery of the CNS after repeated autoimmune bouts and that lung microbiota are external regulators of de- and regenerative processes within the CNS tissue. We aim to identify brain-resident and peripheral targets to prevent permanent CNS damage and/or to foster its recovery which ...

The meninges are an important anatomical checkpoint for CNS autoinflammatory diseases, as this is where immune cells are recruited and where they can chronically persist. We propose that CNS persistent inflammation alters the meningeal milieu, particularly the vessels, creating a chronic inflammatory environment. This sustained inflammation impedes CNS recovery from acute damage. Our research aims to identify, in animal models and human samples of multiple sclerosis, cells and factors in the ...

Since the first funding period, Z02 has provided comprehensive support for all our research projects, from experimental design to bioinformatics data analysis. We specialize in bulk and single-cell genomic methods, including technologies like 10x Genomics and flow-cytometry based isolation methods. Additionally, we offer training on tissue preparation, single-cell sorting, and the use of 10x Genomics equipment to ensure high-quality data. By centralizing sample preparation, sequencing, and analysis, ...

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: ...

Strokes destroy excitatory inputs – not only in the stroke area, but also in remote regions such as the hippocampus, which may lead to disorganized GABAergic activity and cause cognitive decline. We propose here to identify and modulate checkpoints of GABAergic population dynamics shaping microcircuits of excitatory pyramidal neurons in the hippocampus. We aim at enhancing functional and structural rewiring processes by systematically modulating GABAergic interneuron activity and thus defining ...

Neuronal loss in acute or chronic brain disease could be treated by neuronal replacement strategies, such as transplantation of young neurons, if they integrate properly into the existing networks. Here we explore the cell-based and molecular mechanisms causing hyperinnervation and overshoot loss of input connectivity as well as the newly discovered hurdle in output connectivity, the lack of myelination. Candidate as well as unbiased approaches are pursued to identify the critical checkpoints and ...