The Bioimaging and Tissue Analysis Platform Z01 will harness the unique neuropathological and ultrastructural expertise at the Göttingen and Munich sites to provide a platform for integrated tissue analysis. With the focus being on a comparative analysis of human and experimental tissue, Z01 will be crucial to the validation of checkpoints identified in preclinical models in the context of human diseases. Besides supporting the different CRC projects with neuropathological analysis of human tissue samples, Z01 will also provide state-of-the-art correlative light and electron microscopy to elucidate CNS recovery with ultrastructural  resolution. In the first funding period Z01 contributed, e.g., to the analysis of axon pathology as an essential determinant of CNS recovery, of inflammatory mediators as contributors to sculpting a pro-regenerative tissue environment, and of oligodendrocyte-axon interactions as key drivers of remyelination. In the upcoming funding period, our technical developments will focus on applying ATUM-based correlative light and electron microscopy to track recovery processes in the CNS (Aim❶) and on developing AI-supported cellular analysis and spatial transcriptome-based molecular analysis ofarchival human CNS tissue(Aim❷). Specifically, we will cover the following aims:

Aim: Bioimaging platform: To devise correlated electron microscopy techniques for CNS recovery. In this aim, the study of cellular regenerative processes will be enabled in different projects of the CRC by combining light and electron microscopy techniques. In particular, ATUM-based correlative volume electron microscopy will be further developed to identify cellular interactions during CNS regeneration in situ at high resolution. In order to enable an in-depth molecular and morphological description of cellular heterogeneity at sites of progressive pathology or tissue regeneration, novel approaches for correlative analysis of electron microscopy and omics will be developed. Relevant established and novel electron microscopy techniques will be optimized for the application to human CNS tissue.

Aim: Tissue analysis platform: To integrate basic research with unified molecular and cellular human tissue analysis. Here, we will support the “translation” of key experimental findings within projects of the CRC to well characterized human brain tissue (Aim A). This iterative process will be facilitated by an already established open microscopy platform (integrated with the CRC Research Data Platform) allowing data sharing and joint microscopy sessions across the research sites. An in-depth cellular and molecular analysis of human CNS tissue is essential for this process and requires ongoing technological development. This (Aim B) will be obtained by optimizing human brain tissue preservation protocols for spatial transcriptomics supported by a continued neuropathologically inspired adoption of AI-supported image analysis. This will enable to integrate morphological information and gene expression analysis at the cellular level.