LUMICKS C-Trap Edge 350 - PROJECT SUMMARY/ABSTRACT This proposal requests the purchase of a LUMICKS C-Trap Edge instrument for a Major User group at the University of Utah. C-Trap Edge is the first and currently only truly correlative tweezers-fluorescence system combining four core technologies: dual-trap continuous-wave optical tweezers, 3-color TIRF/widefield microscopy, label-free IRM, and intuitive software driven ultra-stable multi-channel micro-fluidics system with automated pressure-driven laminar flow. All combined, the system enables high-resolution single-molecule force- fluorescence measurements with greatly enhanced throughput. Single molecule force and fluorescence spectroscopies have revolutionized cellular and molecular biology, biochemistry, biophysics, and biomedical engineering studies to answer key biological and health-related questions. Currently, these tools are mainly restricted to laboratories with dedicated specific expertise and that have lab-built single molecule instruments. The C-Trap is designed as a turn-key system that allows laboratories without single molecule force or fluorescence spectroscopy expertise to perform state-of-art single molecule force, position, and fluorescence localization and FRET analysis at unparalleled spatial and temporal resolution. Importantly, the intuitive instrument and software interface and automation capabilities will allow non-expert users to run experiments and collect high-quality data after minimal training. The proposal is being submitted on behalf of eight Major Users (all with NIH R01 or R35 funding), who will utilize the bulk of the instrument time, and six Other Users (also all with NIH R01 or R35 funding). These Users represent six departments – Biochemistry, Chemistry, Physics, Microbiology & Immunology, and Mechanical Engineering at the University of Utah, as well as Chemistry & Biochemistry at Utah State University – and span multiple institutions across the state, including the University of Utah and Utah State University. The C-Trap will significantly advance the NIH funded projects of these researchers by enabling high impact single molecule mechanobiological and fluorescence studies on a range of scientifically important biomedical questions in areas or mechanical tension sensing, membrane remodeling, cell motility, nucleic acid packaging and processing enzymes, cell-cell interactions, and protein folding dynamics. The Major Users and technical advisors have extensive relevant expertise with the technology to provide guidance to all Users. The University of Utah are committing significant institutional resources (dedicated space and operating, service, and maintenance funds) to ensure sustained and effective use. The establishment of resource will significantly enhance numerous research programs at University of Utah and contribute to discovery of high impact scientific, biomedical and health-care related knowledge.