Mechanistic and single molecule studies of biological systems using fluorescence-force and label-free hybrid imaging at the University of Edinburgh

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The possibility of holding onto individual cells, microbes or even single proteins opens the road for a small-scale understanding and quantification of forces, torques and mechanics of vital processes such as cell division. Thanks to so-called "optical traps" (synonymous to tweezers we can now use light to grab and manipulate cells and biomolecules using a non-contact force. This revolutionary technology has proved essential in medical applications (eg. sperm manipulation and in vitro fertilization, tissue regeneration), biomedical research (eg. single molecule and single cell manipulation) and studying and engineering biomaterials (eg. hydrogels). Optical tweezers are not limited to what we can see using normal microscopes, can "feel" forces a billion time smaller than weighing an ant on your finger and perform measurements at a temporal resolution that is 100 times faster than you can blink. This unimaginable "super-resolved" information is therefore able to yield unique information on the behavior of single molecules and reveal how they work. This proposal requests funds to purchase the first optical tweezers with fluorescence and label-free microscope in Scotland, to be hosted in the School of Biological Sciences at the University of Edinburgh. This will enable us to: 1) manipulate single cells, bacteria, biomolecules and even viruses;2) measure forces generated during the interaction of, and reactions between, these entities; 3) understand their dynamic and mechanical properties in real time with high spatial resolution. This instrument perfectly sits at the interface between engineering, physical and biological sciences and will allow many groups working on a great diversity of projects to address outstanding questions in their field of research.The optical tweezers with fluorescence/label-free microscope will be housed in a state-of-the-art facility called the Centre Optical Imaging Laboratory (COIL) and will be made available to the wider community of researchers in Edinburgh and Scotland. Researchers at the University of Edinburgh will use this instrument across a broad range of projects such as cell division, cellular transport and organization, bacteria swimming, strength of bacteria biofilms, material properties of DNA hydrogels, formation and stability of proteins and protein condensates that are relevant for cell regeneration and neurodegenerative diseases, folding/unfolding of DNA origami, chromatin organization, genome editing and off-target CRISPR mutations, and others. The acquisition of this technology represents a major step forward as it is currently not available anywhere in Scotland but the demand is increasing rapidly and attracts interest from researchers in diverse fields across STEM. Beyond the academic interest, this instrument will also be used to study industrial and societal problems, such as the interaction between bacteria in water purification systems. Optical tweezers with fluorescence and label-free technology is thus an unparalleled opportunity to advance imaging in Scotland and also in the whole of the UK, where only other 3 similar instruments exist. The outstanding track record of biomolecular research across the various schools in College of Science and Engineering and the expertise in imaging focused in the Edinburgh Super-Resolution Imaging Consortium (ESRIC) and Centre for Optical characteriSation, control and iMagIng of Complex materials (COSMIC) makes Edinburgh University the ideal place where to host it.