STRUCTURAL BIOLOGY SHARED RESOURCE - PROJECT SUMMARY/ABSTRACT The MECCC Structural Biology Shared Resource (SBSR) supports a wide range of technologies for identifying new targets, defining molecular mechanisms, and generating tool compounds and therapeutic leads. Services include: (1) state-of-the-art protein production; (2) high resolution structure determination by X-ray crystallography, NMR and cryo-EM; (3) mass spectrometry-based proteomics analyses; and (4) additional advanced technologies. SBSR provides access to state-of-the-art infrastructure located in-house and at regional centers and national laboratories to support the scientific priorities outlined in the MECCC Strategic Plan. Protein-based tools facilitate the mechanistic dissection of fundamental biological and pathological processes, and the validation of potential therapeutic strategies in cell- and animal-based disease models. Mass spectrometry and proteomics enables the discovery of new targets and biomarkers, and provides deep mechanistic insight into responses associated with disease states and treatment regimens. Structural data provide atomic-resolution insight for protein design and medicinal chemistry essential for enhancing initial hits and lead therapeutics. The SBSR Specific Aims are: 1. Provide state-of-the-art technologies for protein expression, purification and characterization, and validation. These resources include bacterial, insect cell, and mammalian cell expression platforms supported by considerable automation to facilitate these efforts. SBSR staff provide the full range of support services, including construct design and downstream characterization. 2. Enable high resolution structural characterization. Available resources include in-house capabilities in NMR, X-ray crystallography and cryo-EM, as well as extensive access to state-of-the art national facilities for NMR and cryo-EM (New York Structural Biology Center) and X-ray crystallography (Brookhaven National Laboratory and Argonne National Laboratory). SBSR staff provide the full range of support services, including data collection and processing, structure determination, validation, and structure interpretation. 3. Provide state-of-the-art mass spectrometry capabilities for proteomics analyses, including protein abundance, determination of regulated protein pathways and other networks, identification and quantification of protein post-translational modifications and protein synthesis rates. SBSR staff provide the full range of support services, spanning experimental design, sample preparation, data acquisition and data interpretation. The breadth of core services supports the entire spectrum of investigators, and the extensive coordination among the SBSR leaders allows for the seamless movement among core-supported technologies. As such, projects can enter the pipeline at any stage. For example, inexperienced investigators can enter the pipeline at the protein expression stage and receive suppo...