UNIVERSITY ILLINOIS BRAIN INITIATIVE GRANTS AND OTHER UNIVERSITY ILLINOIS GRANTShttps://grantome.com/grant/NIH/U01-MH109062-02

UNIVERSITY ILLINOIS BRAIN INITIATIVE GRANTS AND OTHER GRANTS
https://grantome.com/grant/NIH/U01-MH109062-02

The BRAIN Initiative seeks to understand the spatial, temporal and chemical nature of the brain. RFA-MH-15- 225 calls for the development of new tools and technologies with a number of goals, including methods to obtain cell type and chemical information from individual cells and their connections. While many imaging approaches exist that use specific probes to image subsets of cells and their interconnections, this project will create a chemical information-rich approach that advances the emerging technique of stimulated Raman scattering microscopy (SRSM). SRSM provides vibrational spectral data from every location of a living brain slice so that dynamic chemical changes can be followed. The Raman spectra contain tremendous chemical information but the data is coded in complex overlapping molecular vibrational bands. With appropriate training sets-derived from the Raman data and comparing it to the chemical contents of individual cells-a series of mathematical models will be developed that create unlimited Computational Histology maps. In order to (a) inform the mathematical model in the development phase and (b) greatly augment the chemical information obtained from these studies, dissociated cells will be subjected to another measurement-high throughput single cell mass spectrometry (MS)-on tens of thousands of cells. Single cell MS provides detail on hundreds of components in each cell, effectively mapping each cells’ peptidome and metabolome. The MS data includes unique information on the metabolic state of these cells and allows us to define known and unknown cell types. Computational models will be used to correlate the SRSM data to the MS-derived chemical content as well as deliver strategies to examine the dynamic changes and heterogeneity in brain tissue. These technologies will be validated using the dentate gyrus. The focus of the work will be on the hippocampal neurons and glia of the dentate gyrus and their involvement in memory formation, and issues related to astrocyte morphology changes. By performing patch clamp physiological measurements and detailed MS-based metabolomic profiling on the patched cells of the dentate gyrus, the SRSM and single cell MS technology platform will be validated by investigating this complex area of the brain containing many cell types, heterogeneous morphologies, and chemical characteristics. These technologies will provide unmatched detail on the chemical content and dynamics within this defined brain region, answer long intractable questions related to cellular heterogeneity, and relate this information to organization and functional processes such as long term potentiation.

Public Health Relevance

A novel analytical platform, integrating the strengths of mass spectrometry and stimulated Raman scattering microscopy, will be developed to characterize brain cells and tissues with unmatched chemical detail. This technology platform directly addresses an unmet need for the BRAIN initiative, will lead to new neuroscience insights, and help create novel diagnostic and therapeutic opportunities.

  Funding Agency

AgencyNational Institute of Health (NIH)InstituteNational Institute of Mental Health (NIMH)TypeResearch Project–Cooperative Agreements (U01)Project #5U01MH109062-02 Application #9146405Study SectionSpecial Emphasis Panel (ZMH1) Program OfficerFreund, Michelle Project Start2015-09-18Project End2018-06-30Budget Start2016-07-01Budget End2017-06-30Support Year2Fiscal Year2016Total CostIndirect Cost

  Institution

NameUniversity of Illinois Urbana-ChampaignDepartmentTypeDUNS #041544081CityChampaignStateILCountryUnited StatesZip Code61820

  Related projects

NIH 2017
U01 MHBRAIN Initiative: Integrated Multimodal Analysis of Cell and Circuit-Specific Processes in Hippocampal Function
Sweedler, Jonathan V. / University of Illinois Urbana-ChampaignNIH 2016
U01 MHBRAIN Initiative: Integrated Multimodal Analysis of Cell and Circuit-Specific Processes in Hippocampal Function
Sweedler, Jonathan V. / University of Illinois Urbana-ChampaignNIH 2016
U01 MHBRAIN Initiative: Integrated Multimodal Analysis of Cell- and Circuit-Specific Processes in Hippocampal Function
Sweedler, Jonathan V. / University of Illinois Urbana-Champaign$229,147NIH 2015
U01 MHBRAIN Initiative: Integrated Multimodal Analysis of Cell and Circuit-Specific Processes in Hippocampal Function
Sweedler, Jonathan V. / University of Illinois Urbana-Champaign$778,402

  Publications

Do, Thanh D; Ellis, Joseph F; Neumann, Elizabeth K et al. (2018) Optically Guided Single Cell Mass Spectrometry of Rat Dorsal Root Ganglia to Profile Lipids, Peptides and Proteins. Chemphyschem 19:1180-1191Qi, Meng; Philip, Marina C; Yang, Ning et al. (2018) Single Cell Neurometabolomics.ACS Chem Neurosci 9:40-50Neumann, Elizabeth K; Comi, Troy J; Spegazzini, Nicolas et al. (2018) Multimodal Chemical Analysis of the Brain by High Mass Resolution Mass Spectrometry and Infrared Spectroscopic Imaging. Anal Chem 90:11572-11580Neumann, Elizabeth K; Do, Thanh D; Comi, Troy J et al. (2018) Exploring the Fundamental Structures of Life: Non-targeted, Chemical Analysis of Single Cells and Subcellular Structures. Angew Chem Int Ed Engl :Bothwell, Mia Y; Gillette, Martha U (2018) Circadian redox rhythms in the regulation of neuronal excitability. Free Radic Biol Med 119:45-55Comi, Troy J; Neumann, Elizabeth K; Do, Thanh D et al. (2017) microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling. J Am Soc Mass Spectrom 28:1919-1928Seo, Yongbeom; Leong, Jiayu; Teo, Jye Yng et al. (2017) Active Antioxidizing Particles for On-Demand Pressure-Driven Molecular Release. ACS Appl Mater Interfaces 9:35642-35650Comi, Troy J; Makurath, Monika A; Philip, Marina C et al. (2017) MALDI MS Guided Liquid Microjunction Extraction for Capillary Electrophoresis-Electrospray Ionization MS Analysis of Single Pancreatic Islet Cells. Anal Chem 89:7765-7772Do, Thanh D; Comi, Troy J; Dunham, Sage J B et al. (2017) Single Cell Profiling Using Ionic Liquid Matrix-Enhanced Secondary Ion Mass Spectrometry for Neuronal Cell Type Differentiation. Anal Chem 89:3078-3086Comi, Troy J; Do, Thanh D; Rubakhin, Stanislav S et al. (2017) Categorizing Cells on the Basis of their Chemical Profiles: Progress in Single-Cell Mass Spectrometry.J Am Chem Soc 139:3920-3929

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