C-Trap Optical Tweezers System for Single-Molecule Studies - PROJECT SUMMARY / ABSTRACT The goal of this Shared Instrumentation Grant application is to permanently integrate a LUMICKS C-Trap Dymo optical tweezers system into the Structural Biology Core (SBC) at UT Health San Antonio (UTHSA), fulfilling a critical gap in our ability to visualize and manipulate biomolecular interactions in real time. UTHSA’s SBC has long provided regional leadership in structural biology, supporting NIH-funded research through cryo- EM, X-ray crystallography, and NMR. However, over a dozen NIH-funded investigators on campus study intrinsically disordered proteins (IDPs), phase-separated condensates, and force-sensitive macromolecular complexes – systems that cannot be fully resolved using traditional methods. The C-Trap uniquely addresses this limitation by enabling single-molecule interrogation of full-length, dynamic protein and nucleic acid assemblies as they respond to protein binding partners, nucleic acid scaffolds, small molecule ligands, and mechanical forces, all in real time. Already deployed on campus under a temporary lease agreement funded through a collaborative, grassroots effort by three NIH-funded investigators, the C-Trap has catalyzed transformative discoveries in just three months of operation. This model, while unsustainable, has demonstrated the platform’s immediate value and feasibility at UTHSA, enabling high-quality, novel data collection in genome maintenance, transcriptional regulation, and cancer biology. As the first and only C-Trap Dymo system in Texas, its presence has already begun to transform research approaches across our institution. Formal integration into the open-access SBC is urgently needed to expand availability, ensure operational continuity, and unlock its full potential for a growing community of NIH-funded structural, cancer, and cellular researchers. This proposal now seeks to broaden access by embedding the C-Trap within the SBC, where it will enhance training capacity, sustainability, and resource sharing across UTHSA, the University of Texas System, and regional collaborators. It will also complement cryo-EM, NMR, and X-ray capabilities already housed in the SBC, solidifying UTHSA’s emerging leadership in structural biology and single-molecule biophysics. If funded, the S10 will provide permanent institutional access to the already-installed instrument and support a dedicated staff scientist for operations and user training. With investment in this high-value, high-impact technology, the C-Trap will continue to accelerate scientific discovery, enable cutting-edge experimentation, strengthen the research portfolios of new and established investigators, and expand the state of Texas’s capacity for frontier biomedical research.