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.

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 #
5P41GM103622-22
Application #
9405020
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
22
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Illinois Institute of Technology
Department
Type
DUNS #
042084434
City
Chicago
State
IL
Country
United States
Zip Code
60616
Sharma, Nidhi; Chakravarthy, Srinivas; Longley, Matthew J et al. (2018) The C-terminal tail of the NEIL1 DNA glycosylase interacts with the human mitochondrial single-stranded DNA binding protein. DNA Repair (Amst) 65:11-19
Joureau, Barbara; de Winter, Josine Marieke; Conijn, Stefan et al. (2018) Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3). Ann Neurol 83:269-282
Holcomb, Joshua; Doughan, Maysaa; Spellmon, Nicholas et al. (2018) SAXS analysis of a soluble cytosolic NgBR construct including extracellular and transmembrane domains. PLoS One 13:e0191371
Zhang, Zhening; Liang, Wenguang G; Bailey, Lucas J et al. (2018) Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme. Elife 7:
Garland-Kuntz, Elisabeth E; Vago, Frank S; Sieng, Monita et al. (2018) Direct observation of conformational dynamics of the PH domain in phospholipases C? and ? may contribute to subfamily-specific roles in regulation. J Biol Chem 293:17477-17490
Gonzalez-Martinez, David; Johnston, Jamie R; Landim-Vieira, Maicon et al. (2018) Structural and functional impact of troponin C-mediated Ca2+ sensitization on myofilament lattice spacing and cross-bridge mechanics in mouse cardiac muscle. J Mol Cell Cardiol 123:26-37
Sekula, Bartosz; Dauter, Zbigniew (2018) Crystal structure of thermospermine synthase from Medicago truncatula and substrate discriminatory features of plant aminopropyltransferases. Biochem J 475:787-802
Moyo, Thandeka; EreƱo-Orbea, June; Jacob, Rajesh Abraham et al. (2018) Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J Virol 92:
Ait Mou, Younss; Lacampagne, Alain; Irving, Thomas et al. (2018) Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy. J Mol Cell Cardiol 114:345-353
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

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