A new consortium in Edinburgh will give cell biologists access to every major type of super-resolution microscope currently available, allowing them to watch individual molecules moving and interacting inside living cells at millisecond speeds. This matters because the fundamental units of life—molecules—have been too small and too fast for conventional microscopes to track directly. Biologists have had to infer molecular behaviour from blurry snapshots. The new instruments, built from advances in physics, chemistry, and engineering, will let researchers see exactly where thousands of single molecules go, what they touch, and how they assemble into structures. The consortium also plans to develop the next generation of imaging tools, guided by the biological questions that matter most. If successful, this work will transform understanding of the molecular mechanisms underlying human diseases. It is primarily fundamental science—curiosity-driven research into how cells work at the molecular level. Past investments in similar fundamental imaging technologies have led directly to breakthroughs in drug development, diagnostics, and personalised medicine. Deeper knowledge of molecular behaviour in living cells could eventually reveal new targets for treatments, but the immediate goal is to see what has been invisible.
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Recently, the detail with which biologists can examine microscopic samples has increased dramatically. Improvements in this microscopic 'resolution' can be split into; temporal (the speed with which biologists can look at fast changing things) and spatial (the size of objects, or spacing between them). Recent advancements in technology, combined with some clever biology, means that we can, for the first time, determine the precise positions of many 10000s of single molecules, their interactions, movements and formation into structures within living cells, with millisecond (1000s of frames of a 'movie' per second) rates. As molecules are the fundamental units of cells, and cells are the minimal units of life, increases in resolution are starting to revolutionise our understanding of cell biology by examining directly the molecular workings of cells. The technological improvements that make this possible have come from the physical sciences: mathematics, physics, chemistry as well as engineering. To continue with this progress, the UK scientific community needs to bring the best cell biologists with the most appropriate biological tools and questions, together with researchers at the cutting edge of the physical sciences. Work at the so-called 'Life Science Interface' is not straightforward; it requires extra time for the various researchers involved to speak to each other, specialised infrastructure, a genuine desire to work across traditional scientific boundaries, as well as committed support from both the funders and the institutional management to ensure that these ambitious collaborations can work. To date, few institutions in the UK can claim success in this. Heriot Watt University is well known internationally for its work in the physical sciences particularly. Taking advantage of this, the University established the 'Life Science Interface Laboratory (LSI)' in 2010 with a large investment in both equipment and staff recruitment. Recruiting biologists with a proven track record of working at the interfaces with mathematics, physics and chemistry, a new Research Institute was established, led by cell biologists, to accelerate the interactions between disciplines. This Institute established a close collaboration with the nearby Institute of Genetics and Molecular Medicine (IGMM), known for its advanced biology aimed at addressing the molecular mechanisms that underly human disorders and diseases. This collaboration is proving very productive, with many small-scale pilot projects under-way investigating the use of the new 'super-resolution' imaging techniques described above, applied to cutting-edge biological questions in human healthcare. Here, we are requesting support for new equipment and technical support to bolster this collaboration. Three new microscopes are requested, which will allow more cell biologists to 'see' structures and molecules in their samples in unprecedented detail. Combined with the facilities at the LSI at Heriot Watt, the 'Edinburgh Super-Resolution Imaging Consortium' (ESRIC) will bring together every single currently available live cell super-resolution imaging approach, together with world-leading cell biologists and physical scientists and engineers with a proven track record of cross-disciplinary successes; something unique in the UK. We are also requesting funding to pursue research across ESRIC, which will in addition be made openly available to a large number of cell biologists across Edinburgh. Importantly, simply purchasing new commercially available microscopes is not the limit of our ambition; the engineers and physicists in our consortium, directed and informed by cell biologists, are already developing the 'next generation' of imaging approaches that will be necessary to continue progress in biological discovery: of equal importance, the senior management of all the Institutes in ESRIC are demonstrably committed to this activity.
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