The BioCAT Biotechnology Research Resource operates X-ray beamline 18ID at the Advanced Photon Source, Argonne National Laboratory. Now in its 20th year of operation, it is a mature, productive facility with many capabilities unique in the USA, and, arguably, the world. Going forward, we intend to maintain our world- class capabilities in static, time- and spatially-resolved fiber diffraction with beamline enhancements for increased flux and beam quality. A novel high speed, high sensitivity, high spatial resolution pixel array detector will provide an excellent match to the needs of our muscle diffraction program. Also proposed is a versatile micro-diffraction/micro-SAXS instrument that can use one of two Compound Refractive Lenses optimized for either wide- or small-angle fiber crystallography, and continuous flow SAXS experiments. We will implement multimodal scanning micro-diffraction, x-ray florescence microscopy, phase contrast and uv/visible imaging that can be done either singly or in combination with the same instrument on the same samples. Developments in time-resolved SAXS will extend available time regimes from 500 ns to seconds with major reductions in sample consumption, by more than order of magnitude, from current capabilities. This will allow a much wider range of biomedical problems to be addressed than previously possible. A new beamline data acquisition and control system will provide a common interface and better data management for all experiments and advanced support for time resolved experiments. Combined refractive index, dynamic light scattering and multi-angle light scattering measurements with SAXS will offer more comprehensive sample characterization on-line for more robust results. A multi-scale modeling effort will allow extracting more information from muscle X-ray diffraction studies. The proposed developments in multi-scale simulations for interpreting single molecule SAXS data will profoundly benefit studies of multicomponent systems that show considerable conformational heterogeneity. Our relationship with the CCP-SAS project will enable us to widely disseminate the advanced modeling tools we create to not only all our DBP's, collaborative and service users but to the wider biomedical community. Our Driving Biomedical Projects, collaborative, and service projects have relevance to basic mechanisms of muscle function, heart disease, retinitis pigmentosa, cancer and neuro-degenerative diseases. Our proposed training activities are designed to ensure safe, efficient and productive use of the resource by our users. Our proposed dissemination activities are designed to grow our user community by keeping targeted biomedical communities well-informed of resource capabilities.
TheBiophysicsCollaborativeAccessTeamusesintenseX-?raybeamsfromthe AdvancedPhotonSource,ArgonneNationalLaboratorytoperformbasicbiomedical researchonnon-?crystallinebiologicalmaterials.Resultsofthisresearchare expectedtoberelevanttoheartdisease,arthritis,cancer,andproteinmisfolding diseasessuchasAlzheimer'sandALS.
|Ruszkowska, Agnieszka; Ruszkowski, Milosz; Dauter, Zbigniew et al. (2018) Structural insights into the RNA methyltransferase domain of METTL16. Sci Rep 8:5311|
|LaRochelle, Jonathan R; Fodor, Michelle; Vemulapalli, Vidyasiri et al. (2018) Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition. Nat Commun 9:4508|
|Ma, Weikang; Gong, Henry; Kiss, Balázs et al. (2018) Thick-Filament Extensibility in Intact Skeletal Muscle. Biophys J 115:1580-1588|
|Ma, Weikang; Gong, Henry; Irving, Thomas (2018) Myosin Head Configurations in Resting and Contracting Murine Skeletal Muscle. Int J Mol Sci 19:|
|Malaby, Andrew W; Das, Sanchaita; Chakravarthy, Srinivas et al. (2018) Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors. Structure 26:106-117.e6|
|Zhou, Bing-Rui; Jiang, Jiansheng; Ghirlando, Rodolfo et al. (2018) Revisit of Reconstituted 30-nm Nucleosome Arrays Reveals an Ensemble of Dynamic Structures. J Mol Biol 430:3093-3110|
|Yuan, Chen-Ching; Kazmierczak, Katarzyna; Liang, Jingsheng et al. (2018) Sarcomeric perturbations of myosin motors lead to dilated cardiomyopathy in genetically modified MYL2 mice. Proc Natl Acad Sci U S A 115:E2338-E2347|
|Anderson, Robert L; Trivedi, Darshan V; Sarkar, Saswata S et al. (2018) Deciphering the super relaxed state of human ?-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers. Proc Natl Acad Sci U S A 115:E8143-E8152|
|Riback, Joshua A; Bowman, Micayla A; Zmyslowski, Adam et al. (2018) Response to Comment on ""Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water"". Science 361:|
|Korasick, David A; Campbell, Ashley C; Christgen, Shelbi L et al. (2018) Redox Modulation of Oligomeric State in Proline Utilization A. Biophys J 114:2833-2843|
Showing the most recent 10 out of 143 publications