MICA: A super resolution optical microscopy facility at the MRC Laboratory of Molecular Biology.

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Light microscopy plays an indispensable role in modern biomedical research. By providing the ability to visualise specific processes within healthy and diseased cells, often in real-time, this technique has been a driving force in increasing our knowledge of biological processes. This knowledge is, of course, essential for developing new strategies for the diagnosis and treatment of specific human diseases. Until recently, light microscopy has been hampered by the so-called "diffraction limit". This is a theoretical limit to how far two objects need to be apart before they can be resolved by the microscope, and is typically in the region of half the wavelength of visible light (~ 250 nanometers (nm), or 1/4000th of a millimetre). Many important biological structures within our cells are smaller than 250nm and therefore remain poorly characterised. These structures include the "organelles" that perform specific cellular functions and the membrane-bound carriers and filaments along which trafficking occurs, as well as infectious viruses. Several microscopy techniques have been developed in the last few years that allow the diffraction limit to be bypassed, thereby providing access to previously unappreciated processes within cells. These 'super resolution" (SR) methods-some of which allow specific molecules to be localised with a precision of up to ten times greater than conventional microscopy-promise to revolutionise biomedical research, particularly when combined with other techniques in which the UK has pre-established expertise.Two MRC-funded research organisations in Cambridge-the Laboratory of Molecular Biology (LMB) and Mitochondrial Biology Unit (MBU)-are proposing to jointly establish a multi-user centre of innovation in applied super resolution (SR) optical microscopy. Scientists at LMB and MBU have made, and continue to make, major discoveries into fundamental biological processes and have frequently translated them into commercial and therapeutic successes. There is a remarkable track record of studying biological processes at the scale of the structure of individual proteins and protein complexes, as well as at the cellular level. SR platforms would close the gap between these molecular and cellular studies, allowing multi-scale analysis of cellular processes and the relationship to disease in a world-renowned research environment. The critical importance of light microscopy to LMB and MBU is demonstrated by the presence of > 20 highly used confocal or wide-field microscopes, until recently the highest quality optical microscopes available. Ready access to SR microscopy will make a major impact on the productivity of the organisations. Indeed, 26 groups within the LMB and MBU have projects that require specific SR platforms. Their needs can only be fulfilled by providing three different, leading SR systems: structured illumination, single molecule localisation microscopy (e.g. PALM/STORM) and stimulated emission depletion (STED) microscopy. These systems have non-overlapping strengths and different projects require different systems.Substantial added value will be provided by (i) capitalising on the highly successful research programmes and complementary technological expertise within the partner organisations, (ii) building on pioneering biotechnology developed at LMB to develop superior labelling methods for SR techniques, (iii) strong collaborations with industrial partners and (iv) provision of access to other, local users to facilitate their research and foster collaborations with LMB and MBU. The project is sustainable. It builds on well-established infrastructure for management of microscopy resources and user training, and includes early access to new developments through the establishment of industrial partnerships and a significant financial commitment from LMB and MBU. There is also a strong component of cultivating the next generation of scientists by providing training in SR techniques.