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 uniqu 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

Public Health Relevance

TheBiophysicsCollaborativeAccessTeamusesintenseX-?raybeamsfromthe AdvancedPhotonSource,ArgonneNationalLaboratorytoperformbasicbiomedical researchonnon-?crystallinebiologicalmaterials.Resultsofthisresearchare expectedtoberelevanttoheartdisease,arthritis,cancer,andproteinmisfolding diseasessuchasAlzheimer'sandALS.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103622-23
Application #
9625778
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wu, Mary Ann
Project Start
1997-09-30
Project End
2020-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
23
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Illinois Institute of Technology
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
042084434
City
Chicago
State
IL
Country
United States
Zip Code
60616
Korasick, David A; White, Tommi A; Chakravarthy, Srinivas et al. (2018) NAD+ promotes assembly of the active tetramer of aldehyde dehydrogenase 7A1. FEBS Lett 592:3229-3238
Kiss, Balázs; Lee, Eun-Jeong; Ma, Weikang et al. (2018) Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle. Proc Natl Acad Sci U S A 115:10369-10374
Huang, Wei; Peng, Yi; Kiselar, Janna et al. (2018) Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains. Nat Commun 9:3520
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

Showing the most recent 10 out of 143 publications