A new microscope at the University of Southampton will resolve structures as small as 30 nanometres—roughly one-thousandth the width of a human hair—in living cells and tissues. Standard light microscopes are physically unable to see details smaller than about 200 nanometres, a barrier set by the diffraction of light. This means researchers cannot directly observe the nanoscale machinery inside cells: the clusters of receptors on immune cells, the tangled networks of neuronal synapses, or the filaments that give lung tissue its elasticity. Without that view, fundamental questions about memory, ageing, immune responses, and disease mechanisms remain unanswered. The instrument, a commercial STED (stimulated emission depletion) microscope, will sit in an open-access core facility serving more than 50 research groups. It will allow biologists, physicists, and engineers to image everything from 2D cell cultures to whole embryos and organoids, live or fixed. The work is fundamental science: it aims to reveal how cells organise themselves at the nanoscale. Past investments in such imaging tools have repeatedly uncovered mechanisms—such as the architecture of synaptic proteins or the dynamics of mitochondrial fission—that later informed drug targets and diagnostic strategies.
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Context Light microscopy is fundamental to biological research, with widefield and confocal fluorescence microscopy being primary techniques in cellular biology. These methods employ fluorescent probes to provide multichannel, multidimensional and functional information by tagging cell types, cellular compartments, organelles and biomolecules etc. However, spatial resolution is restricted by the diffraction limit of light microscopy (determined by the laws of physics) to approximately 200nm laterally (XY) and 600nm axially (Z), which is inadequate to explore the subcellular details vital for comprehending cellular functions, processes and dynamics, inter- and intra-cellular communication, disease mechanisms, and therapeutic optimisation. Over the past two decades, super-resolution microscopy (SRM) has emerged to overcome these limitations, offering access to the sub-cellular nanoworld. Initially confined to specialised laboratories due to technical complexity, some SRMs are now turnkey, with enhanced accessibility, user-friendliness, adaptability, and features, making them suitable for core facility deployment and for the study of diverse sample types. This benefits a wide scientific community across multiple research fields who require organisational and functional information at the nanoscale. SRM stands as the gold standard in fluorescence microscopy, and lack of availability at the University of Southampton (UoS) significantly impedes the advancement of research agendas. Research Enabled Stimulated Emission Depletion (STED) SRM reveals the nanoworld with resolution to 30nm (XY) and 100nm (Z), dramatically extending imaging capability for diverse samples including 2D and 3D cultures, tissues, embryos and organoids; live or fixed. It greatly extends research in diverse fields at UoS spanning biotechnology, neurobiology, immunology, respiratory biology, stem cells and regenerative medicine, ciliary function and microbiology. It addresses fundamental biological questions including (i) neuronal synapse networks, contributing to the understanding of memory, learning, and reaction mechanisms (ii) the role of autophagy in age-related visual degeneration (iii) mitochondrial function and dynamics in health, ageing and disease (iv) receptor clustering and its role in agonism of immunomodulators, (v) collagen supramolecular assembly and its effects on lung tissue biomechanics (vi) Structure and function of cilia in health and disease. All necessitate immediate access to nanoscale 3D imaging to reveal sub-cellular information and keep UoS at the forefront of UK biological research. Aims and Objectives Acquisition of turnkey 3D-STED SRM by the Biomedical Imaging Unit (BIU) at UoS, an open-access, imaging core facility specialising in multimodal, multidimensional, multiscale and correlative imaging, to address multiple, unmet research needs aligned to BBSRC’s strategic objectives. Its impact addresses BBSRC priorities within the Advancing Frontiers of Bioscience and Tackling Strategic Challenges portfolios, extending across and beyond UoS. It would immediately, positively impact a large, interdisciplinary and regional user base (> 50 groups). Applications and Benefits (1) Training the Next Generation: locating STED in an open-access core allows the widest range of undergraduate and postgraduate students, postdocs, early career researchers (ECRs), academics and Research Technical Professionals (RTPs) to benefit through mentored access, training, and ongoing advice and support from project design through to publication. This fosters career development and transferable skills and enhances UoS’s doctoral training programs, ensuring a robust talent pipeline equipped with the expertise needed to drive innovative solutions and advances in cellular biology. (2) Interdisciplinary research collaborations: a step change in image resolution fosters greater synergy by breaking down traditional biology/ physics/ chemistry boundaries and cultivates a dynamic research ecosystem which collectively addresses complex biological questions.
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