A single-cell gene expression microscope in Norwich is currently booked six months in advance, and researchers want a second machine to keep up with demand. Standard single-cell techniques require breaking tissues apart, which destroys all information about how cells are arranged and interact. Spatial transcriptomics keeps tissues intact, allowing scientists to see which genes are active in each cell while preserving their original positions. This matters because a cell’s function depends heavily on its neighbours—a heart cell behaves differently when surrounded by scar tissue, for example. The existing platform has already produced data on gene expression in developing wheat spikelets, and demand spans plant science, mammalian biology, and disease research. If funded, the new machine will double throughput and handle larger tissue sections. For plant breeders, this could reveal how cellular architecture determines crop traits like grain size or disease resistance. For clinical scientists, it could show how tissue organisation changes in disease. The project is primarily about building research infrastructure—it enables fundamental biology rather than delivering an immediate application—but that fundamental understanding of how cells organise themselves has historically underpinned advances in agriculture and medicine.
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Single-cell technologies have become a transformative tool in our understanding of genome regulation and cellular differentiation, across species and in healthy and diseased systems. However, the vast majority of current single-cell approaches involve the dissociation of cells and tissues, losing any insight into how cellular organisation and interactions contribute to tissue architecture. Recent advances have enabled transcriptional heterogeneity in cells to be studied at single-cell resolution while maintaining tissue architecture or positional information. These techniques, collectively termed Spatial Transcriptomics (ST), have the potential to bring much needed biological context to single-cell studies, by revealing not only the differences in gene expression between cells, but by identifying patterns in cell-cell interactions and organisation that contribute to tissue architecture and function. Spatially resolved transcriptomics was highlighted as Nature Methods method of the year in 2020; however commercial platforms with single-cell resolution have only recently becoming available. These methods are currently demonstrating widespread applicability in biology, across many living systems, from microbes to plants to human disease. At EI we have been early adopters of this technology, being the first in the UK to purchase a Vizgen Merscope in 2023. This platform has already delivered transformative research, notably in generating spatially resolved single-cell gene expression data in developing wheat spikelets (https://doi.org/10.1101/2024.12.19.629411), although we have ongoing projects in other plant and mammalian systems. We have seen substantial and widespread demand for access to this platform, from many areas of biological research and from across the UK, to the point where our existing platform is currently booked up to six months in advance. With this application, we propose to increase our capacity by provision of a Vizgen Merscope Ultra to augment our capability to deliver an advanced spatial transcriptomics platform for the UK bioscience community. The provision of this platform will enable us to double our throughput but also work with larger tissue sections, supporting a wide array of projects in diverse biological systems. In particular we will support collaboration and service provision in the plant sciences and other non-model systems, building the expertise EI and the wider Norwich Research Park has in this area. The beneficiaries of this work include researchers and in particular research technical professionals who will gain experience in the application of cutting edge technologies, and deliver transformative and impactful research in their areas of interest; computational scientists who will use the data generated to formulate new approaches for the management, visualisation and interpretation of this data, and practitioners including crop breeders and clinical scientists who will generate novel insights in the architecture of cellular systems and their impact on organism phenotype and disease. By establishing a centralised capability for spatial transcriptomics, with strong institutional track-record and support in service delivery for the wider community, coupled with our teams expertise in technology development and implementation in cellular genomics, we believe this proposal represents a timely and valuable addition to the UK bioscience landscape.
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