In Situ Sequencer for High-Resolution Spatial Transcriptomics

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556014887

The Julius Maximilians University Würzburg (JMU) would like to equip the Single-Cell Center Würzburg, the collaborative unit for experimental single-cell genomics and spatial transcriptomics, with a multiplexed in situ sequencing platform to perform biomedical research. The quantitative measurement of cellular phenotypes in tissues is essential to understand how pathologies are developing. Over the last ten years, the technology for multiplexed spatial quantification of gene expression in tissue sections has developed rapidly, providing an unprecedented resolution, sensitivity and throughput. In situ sequencing is recognized as a superior strategy to characterise tissue architecture at cell type resolution due to its improved signal-to-noise ratio compared with alternative techniques. The method is compatible with fresh-frozen and formalin-fixed paraffin-embedded tissue sections, and, hence, applicable even to lower quality biobank material, can be multiplexed with conventional protein immunohistochemistry and can provide a screening capacity of hundreds of thousands of cells. Robust and versatile commercial platforms are emerging allowing to dispatch in situ sequencing-based spatial transcriptomics at large scale. Researchers in the field of Immunology, Oncology, Cardiology and Infection at JMU would strongly benefit from this platform in order to investigate the crosstalk of cell types with their tissue microenvironment, which influences the regulation of cell states and functions. At the Institute of Systems Immunology (WüSI), researchers focus on the interplay of immune cells with non-immune tissue cells across a variety of immune- and non-immune tissues, and the tissue context strongly impacts immune cell differentiation and function in health and disease. At the Mildred Scheel Early Career Center, scientists will leverage spatial sequencing to investigate the developmental processes of cellular transformation. In the field of Cardiology, spatial transcriptomics will allow to unravel the complex interplay between cardiac cells, fibroblasts and immune cells. Finally, in the field of Infection, the scientists of the Institute of Molecular Infection Biology will investigate the fundamental principles of infection foci organisation. In situ sequencing will play a major role for the success of current and future research consortia such as Collaborative Research Centers located in Würzburg in the field of immuno-cardiology (SFB1525) and infection (SFB1583) and clinical initiatives such as the NCT WERA (Nationales Centrum für Tumorerkrankungen). Altogether, the JMU hosts state-of-the-art expertise in experimental and computational single-cell analysis and will strongly benefit from an in situ sequencing platform for spatial transcriptomics.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: In Situ Sequenzer für hochauflösende räumliche Transkriptomik
• Instrumentation Group: 3150 DNA-Sequenzer
• Applicant Institution: Julius-Maximilians-Universität Würzburg
• Leader: Professor Dr. Dominic Grün