Project Summary We are seeking funding to procure an Aberrior FACILITY Line Stimulated Emission Depletion (STED) super- resolution microscope system. This equipment will bolster the research efforts of 13 NIH-funded scientists at the University of Texas Health Sciences Center (UTHealth) in Houston and the MD Anderson Cancer Center (MDACC), spanning across six departments within the McGovern Medical School (MMS) at UTHealth and one at MDACC. The instrument will introduce a unique, high-resolution multi-color nanoscopy capability to the MMS and the broader Texas Medical Center, as the first of its kind in the region. The cutting-edge STED imaging system can achieve up to 20 nm lateral (xy) and 70 nm axial (z) resolutions, maintaining these resolutions to a depth of up to 80 μm into tissue samples. These features will provide our research community with unparalleled nanoscale imaging, filling a crucial gap in our existing methodologies. Specifically, the microscope will be invaluable for studies demanding high-resolution imaging of complex cellular and tissue structures at molecular scales, where other super-resolution techniques often fall short. The Aberrior FACILITY Line attains excellent resolution with its innovative easy3D STED technology, and its matrix detector array with over 20 avalanche photodiodes improves image clarity by minimizing out-of-focus light; utilizes Adaptive Optics with a flexible mirror to correct for lateral and axial optical aberrations resulting from refractive index variations within the sample; and mitigates photobleaching through adaptive illumination that concentrates the excitation/depletion exclusively where a signal is detected. The microscope will be housed in a dedicated room within the Center for Advanced Microscopy, a UTHealth Shared Resource, located in the medical school building. The imaging core’s full-time staff will facilitate maintenance and user training, supplemented by the FACILITY Line's auto-alignment feature for optimal alignment of the excitation and STED depletion beams with the pinhole. The institution has pledged to cover 10% of the instrument's purchase cost and 100% of the 5-year service contract cost. This support will enable low fee-for-use operation, while maintaining at least 10% of peak usage availability for non-S10 users. Additionally, up to 10% of usage will be allocated free of charge to support junior or un-funded investigators. The investigators who stand to benefit from the proposed instrument are engaged in research spanning a wide range of health and disease areas. Regardless of their focus, they all share a need to investigate biochemical processes and molecular mechanisms at nanoscale, beyond the diffraction limit. The STED system will not only further their innovative work, but also augment the suite of tools accessible to the broader research community, thus enriching research pursuits at UTHealth Houston and the Texas Medical Center. In summary, we are requesting funds to ...