Vanderbilt Center on Mechanobiology LUMICKS C-Trap

About This Grant

PROJECT SUMMARY/ABSTRACT This proposal requests funds to acquire a LUMICKS C-Trap Dymo300 microscope to support NIH-funded investigators across multiple schools at Vanderbilt University. The C-Trap combines the ability to exert forces on molecules and cells through optical tweezers with the ability to visualize structures through confocal imaging with the sensitivity to detect single molecule fluorescence. The instrument is highly automated and capable of handling complex calibrations and work-flow scripts, facilitating access for a broader scientific community. The instrument also includes a microfluidic laminar flow platform that aids in assay construction and protocol refinement. This microscope will be located within, and maintained by, the Vanderbilt Center on Mechanobiology – an initiative that serves faculty labs within the School of Engineering, the School of Medicine Basic Sciences, and the College of Arts and Sciences. All three schools have provided matching financial commitments that will fully cover the service contract for the instrument. Multiple scientific thematic areas have been identified that will specifically benefit ~19 major and minor users from all three schools. Among these themes, Vanderbilt has a strong community of investigators focused on advancing our understanding of DNA repair, replication and gene regulation. These researchers will use the microscope to observe how purified multiprotein machines process and maintain the information encoded within DNA through binding, translocation, and remodeling events. A second theme supports Vanderbilt’s robust cytoskeletal and cell mechanics research programs. In this area, the C-Trap is ideal for visualizing and manipulating actin and microtubule filaments, along with their associated proteins and molecular motors. These studies will provide access to a whole new frontier for Vanderbilt investigators who can deeply probe complex associations among cellular machinery. A third theme will investigate the mechanobiology of T-cell receptor-antigen quality and T-cell activation, as well as other receptor- ligand associations and conformational motions. Additional areas of research involve membrane dynamics, biomolecular condensates, forces associated with phase separation and colloids, and studies of AAA+ protein machines that carry out a multitude of cellular processes. The microscope will serve as a regional resource and bolster teaching across all three schools. The C-Trap will be housed in a space where Vanderbilt has purposefully clustered mechanobiology faculty labs and positioned other core resources. Management, support of the microscope and projects, and long-term operation and maintenance of the system will be led by Dr. Matthew Lang, who has over two decades of experience in optical tweezers and single-molecule studies. Collectively, Vanderbilt is ideally positioned to make rapid and significant use of these new capabilities, extending our research scope across a broad range of NIH-sponsored studies.