The Core Facilities organisational unit of MedUni Vienna, headed by Johann Wojta, has been awarded a grant worth €2.3 million for the project "HighWay2Cell - a platform for high resolution single cell omics" as part of the Austrian Research Promotion Agency's 2022 R&D infrastructure funding call. The platform will enable researchers to elucidate the spatial aspects of cell type heterogeneity and cell-cell interactions in diseased and healthy tissue samples by testing for the presence of a variety of proteins and the expression of hundreds to thousands of transcripts of proteins with up to subcellular precision.
The concept for this project and the successful proposal were developed in the Core Facilities in collaboration with Martin Bilban (Genomics), Sophia Derdak (Bioinformatics), Klaus Kratochwill (Proteomics) and Philipp Velicky (Imaging). From the IT Systems & Communications (ITSC) side, Bernhard Lorenz contributed to the proposal.
The grant will allow to establish a multi-technology, high-throughput platform for spatial analysis of RNA and protein expression in biological samples at the single cell level at the Core Facilities. The platform will include imaging, single-molecule hybridisation and supporting single-cell proteomics technology, enabling the analysis of spatial gene and protein expression at the subcellular level.
In addition to equipment acquiring the molecular measurements, a high performance computing cluster for data analysis can now be implemented in collaboration with the ITSC of the Medical University of Vienna.
For research projects in almost all areas of biomedicine, especially personalised and precision medicine, there is an urgent need to correlate gene expression with protein expression patterns and their respective localisation in individual cells and in tissues. With this knowledge, it is possible to better assess the influence of the microenvironment on physiological and pathological processes of cell regulation and, for example, to detect degenerative diseases or to study the development of tumours at the subcellular level. So far, such measurements have been made at the Core Facilities using Visium technology (10x Genomics), which, however, currently does not have the resolution to provide gene expression at either the single cell or subcellular level. At the proteome level, no analyses of single cells have been possible so far.
The "HighWay2Cell" platform will enable researchers to elucidate the spatial aspects of cell type heterogeneity and cell-cell interactions in diseased and healthy tissue samples by allowing to study the presence of a variety of proteins and the expression of hundreds to thousands of transcripts of proteins with up to subcellular precision. Powerful computational resources will enable integrative analysis of the resulting data, maximising knowledge gains from these experiments. To this end, the following components will be procured with the project funds:
The intended in-situ Single Cell Spatial Transcriptomics component is a complete end-to-end solution, including a fully automated instrument for high-throughput analysis, enabling in-situ visualisation and quantification of gene expression in native as well as formalin-fixed tissue sections at the subcellular level.
The device planned for Spatial Proteomics enables multiplexed immunofluorescence imaging using light microscopy. It allows fully automated acquisition and analysis of dozens of markers on a single sample. This minimises both work time and sample material while allowing the identification of a variety of cell types and their protein expression patterns in situ.
To enable proteome analyses at single cell level for the first time at Medical University of Vienna, this grant will establish an isolation platform for high-precision single cell isolation and dispensing in real time based on picolitre dispensing technology combined with modern image processing. The system will be coupled with existing and future high-performance mass spectrometry systems to enable proteomic analysis of single cells. These data represent a significant extension of the transcriptome analyses that have been possible so far, as, for example, the presence of protein isoforms and post-translational modifications can be investigated.
The envisaged High Performance Computing Cluster will be built by the ITSC and will be connected to the existing High Performance Computing infrastructure (HPC-[GPU] Cluster) operated by the ITSC. This computing cluster will close a gap in terms of universally accessible and centrally managed computing resources at the Medical University of Vienna and make the Medical University of Vienna fit for the age of Big Data and digital and personalised medicine. This infrastructure will provide Core Facilities users with access to high-performance computing resources for independent downstream analysis of experiments including large genomic, transcriptomic, proteomic and cytometric datasets performed in the Core Facilities. Together with the ITSC, the Core Facilities will hereby provide a high-performance computing infrastructure that will be available to all users of the Core Facilities for the analysis of data generated on Core Facilities instruments and to all researchers at the Medical University of Vienna for the analysis of large data sets.