An open-access Spatial Biology Platform for inter-disciplinary studies of human disease

Every organ is the result of a complex structure known as the microenvironment. Our understanding of how disease changes the tissue microenvironment remains limited. One challenge in studying disease related changes in the microenvironment is that we often lose understanding of tissue location - spatial information - when trying to measure many genes or proteins at once. Recent technology advances have overcome this limitation, providing the ability to study gene and protein expression much more reliably without losing spatial information. We wish to purchase equipment incorporating these novel technological advances to establish a Spatial Biology Platform. This will enable us to study gene and protein expression profiles in different regions within the organ, and to relate these changes to what is happening within individual cells. The Spatial Biology Platform will be sited in the Biomedical Imaging Unit of the University of Southampton, an open access facility managed by permanent, senior scientists and technical staff with proven expertise in promoting system productivity, longevity, and uptake. We will apply the Platform to study diseases with significant unmet need for which we have large biobanks of tissue linked to patient outcome data. To maximise the benefit of the platform we will: (i) have dedicated technician and bioinformatic support, (ii) promote inter-disciplinary use of the Platform with engineers and mathematicians including developing 3D maps of human disease, and (iii) establish a regular Spatial Biology Course to train the next generation of scientists and technicians in these approaches.

Improved knowledge of the human tissue microenvironment is essential to advance understanding of disease pathogenesis, its modelling and therapeutic targeting. Recent technology developments in spatial biology provide the opportunity to non-destructively quantify gene and protein expression profiles of selected regions within tissue, and in parallel to investigate the expression profiles of individual cells within their tissue microenvironment. Successful leverage of these developments requires standardized, reproducible analytical pipelines together with well-characterized human tissue banks linked to disease outcome data. Here, an open access Spatial Biology Platform will be established at the University of Southampton and workflows validated to serve a wide, interdisciplinary user base across the South West. We will purchase the NanoString GeoMx Digital Spatial Profiler (DSP) and CosMx Spatial Molecular Imager (SMI) to enable rapid application to diverse tissue biobanks available in Southampton, to investigate protein and RNA expression in diseases with significant unmet need from the regional tissue scale to sub-cellular resolution. The platform will be hosted in the Biomedical Imaging Unit (BIU), an established, open-access core facility managed by permanent, senior imaging scientists and technical staff with proven expertise, promoting system productivity, longevity, and uptake. The BIU currently provides light, electron and X-ray based imaging which would be integrated with the Spatial Biology Platform to enhance correlative approaches, thus expanding capacity and capability. Technical and bioinformatic support will be dedicated to the Platform so maximising project outcomes. BIU has experience of training the next generation of scientists in state-of-the art methods and will develop a dedicated course in spatial biology. BIU's broad user base, combined with its unique capabilities will enhance inter-disciplinary studies towards the benefit of patient.