Microscopy has evolved through centuries of desire to see the unseen world. Modern technologies have pushed the limits of what's possible, inspiring the field of structural biology. Coupled with advances in biochemistry, scientists can now study the fine details of tiny intruders in the body as well as the molecular culprits of disease. Despite these monumental achievements, human health still suffers from persistent dysfunctions in biological molecules. Through cryo-electron microscopy (cryo-EM) imaging technology we can create more translatable models to uncover the atomic details of macromolecules gone awry. For instance, the tumor suppressor p53 is one of the most popular proteins in cancer research, yet there is little structural information about its complete 3D organization. The Center for Structural Oncology (CSO) at Penn State University is working to address these impactful uncertainties. Using a wealth of cryo-EM resources in the CSO, we capture dynamic snapshots of p53 assemblies while preserving their disease-related context for drug discovery and therapeutic development. With these tools in hand, the CSO is working to engineer new molecular paradigms in creating a world without cancer.

The Association of Biomolecular Resource Facilities (ABRF) members typically work in cores (shared resources) or in support of them. ABRF's mission is to define excellence for shared resources worldwide. While our vision is to accelerate breakthroughs in scientific discovery, ABRF is committed to advancing the integration of technologies, education, communication, and reproducible research in the operations of shared scientific resources worldwide. Our members support best practices, research excellence, and reproducibility in scientific discovery. ABRF promotes a collaborative community that cultivates professional development and technological innovation. This document outlines a number of things about ABRF, including ABRF's mission and value statements, examples of its research groups and activities, an example of an ABRF outreach program to inform and guide the scientific community about optimization of shared resources nationwide, and an example of an international outreach and collaborative program with like-minded colleagues and organizations in Africa.

Low-Z nanocrystalline diamond (NCD) grids have been developed to reduce spurious fluorescence and avoid X-ray peak overlaps or interferences between the specimen and conventional metal grids. The low-Z NCD grids are non-toxic and safe to handle, conductive, can be subjected to high-temperature heating experiments, and may be used for analytical work in lieu of metal grids. Both a half-grid geometry, which can be used for any lift-out method, or a full-grid geometry that can be used for ex situ lift-out or thin film analyses, can be fabricated and used for experiments.

Advancements in high content image analysis have led to an increase in the adoption of these techniques in basic science and clinical research. High-throughput approaches to imaging and image analysis require minimal user interventions, circumventing the often prohibitively time-consuming and unreliable standard manual analysis. In this study, we demonstrate how high content imaging (HCI) techniques, in combination with high content analysis (HCA), can be paired with more traditional manual analysis to quantify both micro- and macro-level features of biopsied tissue sections. High-resolution, full-color images of stained tissue were acquired and stitched together to reconstruct the entire tissue section, which enabled analyses that required accurate identification of a given region's location within the tissue section. A custom region of interest grid was generated that followed the curvature of the tissue. The composite images were used in two separate analyses: tissue layer thickness as a macro-level approach, and nuclei density as a micro-level approach. Ultimately, the flexibility of the HCI and HCA methodologies used in this study allowed for complex analysis of tissue that would not have been otherwise feasible.

Over the past three decades, atomic force microscopy (AFM) has undergone a series of design changes to attain a flat XY scan and stable non-contact mode in ambient atmosphere. AFM has evolved into an ideal method for non-destructive scanning of samples with longer probe tip life, high accuracy, repeatability, and automation. Together with self-optimizing algorithms for scan parameters in the non-contact mode, AFM can become as widely adopted as other microscopies such as optical or scanning electron microscopy (SEM). Even full automation of AFM probe tip exchange is now possible with probe type recognition software and laser beam alignment on the cantilever and position-sensitive photo diode (PSPD). By separating the optics stage from the Z stage, an AFM system can be made with low mechanical noise and improved optical vision.