SHeffield IMAging (SHIMA)

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Imaging has been at the heart of huge leaps in understanding in biology and medicine, from the discovery of bacteria using the first microscopes to neuroimaging to determine brain function. All the advances have been totally dependent on the development of new technologies. This is particularly so for the study of objects too small to be seen by the naked eye, where microscopes are essential. Elucidating how cells function, whether they be from humans, plants, fungi or bacteria requires the ability to be able to see the components that make up the cell, determine their localisation and establish how they move relative to each other. In particular this has been driven by developments in microscopy coupled with the use of probes to fluorescently label molecules inside cells and so be able to localise and track them, giving key insights into processes such as cell division, growth and differentiation. However traditional optical microscopy approaches are limited in resolution to about 200 nm, which prevents the nanoscale visualisation of the myriad smaller structures and processes within the cell. Only very recently have new super-resolution (SR) microscopy approaches been invented to allow resolution down to single molecules. Thus we are at a tipping point, where existing methods and levels of understanding will become rapidly superseded by new approaches. In Sheffield we have been quick to recognise the potential of this opportunity and we are at the forefront of the development of new methods in SR microscopy. This includes building our own microscopes, coupling fluorescence microscopy with other high-resolution approaches and applying these advances to important biological and biomedical questions. We are thus ideally placed to optimally exploit the new SR technology as part of a programme of development integrated with application. The University of Sheffield (UoS) is a well-established centre with great strengths in many aspects of biomedical and biological research that are poised to reap the benefits from the new SR technologies. We propose to establish a world-class centre in SR imaging, entitled Sheffield Imaging (SHIMA), based on our current strengths, the proposed project and a large strategic investment by the University of Sheffield. We will purchase commercial SR systems for both Structured Illumination Microscopy (SIM) and Stochastic Optical Reconstruction Microscopy (STORM) as complementary systems allowing single molecule resolution and live cell imaging. The equipment will be housed in our Light Microscopy Facility (LMF) to allow multiple user access from the outset. SR is an emerging field and so an imaging, development centre will be established to drive forward technological advances, for transfer to the LMF. To enhance technology development we will conduct specific seed projects to produce novel probes for both SIM and STORM, to increase the versatility of the techniques and to increase the speed of STORM to allow live cell imaging in 3D. With commercial partners we will ensure the rapid translation of our developments for the community. An interdisciplinary team will manage SHIMA, ensuring optimal technology development within the context of its direct application. Two SHIMA senior experimental officers (SEOs) will be responsible for interdisciplinary technology development, production of novel probes and establishment of widespread biomedical applications. The SEOs will be responsible for training of users, both internal and external creating a vibrant atmosphere of expert researchers across the University (and beyond) with a seamless interface between technology development and application via the LMF. The UoS is committed to SHIMA not only by a substantial direct investment in the project but also via a wider initiative in imaging to establish Sheffield as a key international centre in SR imaging.