The development of innovative measurement and analysis tools enables new information on brain function, often allowing a range of novel questions to be addressed. Rapidly evolving metabolomics, peptidomics and proteomics tools facilitate new findings in both discovery and targeted modes. The Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling provides high-end 'omics-scale characterization of the small molecules, peptides and proteins for samples obtained from brain sub-regions like defined nuclei and even specific single cells. Our sampling methods allow molecular localization via discrete cell isolation, mass spectrometry imaging, measurement of activity dependent release, and quantitation of level changes as a function of exposure to drugs. We then characterize the most important molecular targets in these samples using metabolomics, peptidomics and proteomics via a broad array of mass spectrometry-based technologies. Finally, we provide the critical expertise for capturing the value of data via expert bioinformatics support that integrates disparate data types, develops advanced analytical approaches for complex metabolomics and proteomic experiments, and provides community support through several web platforms. At the beginning of the next granting period, we will be supporting an initial group of 17 major users representing 23 separately funded research projects across the fields of neuroscience, including projects targeting neuropeptides, transmitters and proteins that are involved in multiple aspects of drug escalation, exposure and addiction. We also will address fundamental questions of neuron/glia communication, dendritic protein expression and neuronal plasticity. The Neuroproteomics and Neurometabolomics Center on Cell- Cell Signaling is divided into three scientific cores: Sampling and Separation, Molecular Profiling and Characterization, and Bioinformatics and Systems Biology (plus an Administrative Core). The high level of synergy between the neuroscientists and technologists affiliated with the Center ensures progress in our broad suite of supported research projects, and promises continued advancements in the knowledge of how systems of neurons interact in both the healthy nervous system and upon exposure to drugs of abuse Lastly, a series of outreach initiatives assures that our protocols and approaches are broadly available to the appropriate scientific communities.

Public Health Relevance

Literally hundreds of thousands of chemically distinct entities are present in every cell in the brain and can be modified based on exposure to drugs of abuse, and yet the technologies to measure and follow such chemical complexity are not broadly available. Our Center offers unparalleled measurement capabilities and analytical support to a broad range of drug abuse and fundamental science projects ensuring their success.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Center Core Grants (P30)
Project #
5P30DA018310-15
Application #
9491767
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Rapaka, Rao
Project Start
2004-08-23
Project End
2019-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
15
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Neumann, 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 :
Welle, Theresa M; Alanis, Kristen; Colombo, Michelle L et al. (2018) A high spatiotemporal study of somatic exocytosis with scanning electrochemical microscopy and nanoITIES electrodes. Chem Sci 9:4937-4941
Zheng, Jianbin; Chen, Long; Skinner, Owen S et al. (2018) ?-Glucocerebrosidase Modulators Promote Dimerization of ?-Glucocerebrosidase and Reveal an Allosteric Binding Site. J Am Chem Soc 140:5914-5924
Zhang, Guo; Yuan, Wang-Ding; Vilim, Ferdinand S et al. (2018) Newly Identified Aplysia SPTR-Gene Family-Derived Peptides: Localization and Function. ACS Chem Neurosci 9:2041-2053
Checco, James W; Zhang, Guo; Yuan, Wang-Ding et al. (2018) Aplysia allatotropin-related peptide and its newly identified d-amino acid-containing epimer both activate a receptor and a neuronal target. J Biol Chem 293:16862-16873
Monroe, Eric B; Annangudi, Suresh P; Wadhams, Andinet A et al. (2018) Exploring the Sea Urchin Neuropeptide Landscape by Mass Spectrometry. J Am Soc Mass Spectrom 29:923-934
Checco, James W; Zhang, Guo; Yuan, Wang-Ding et al. (2018) Molecular and Physiological Characterization of a Receptor for d-Amino Acid-Containing Neuropeptides. ACS Chem Biol 13:1343-1352
Do, Thanh D; Checco, James W; Tro, Michael et al. (2018) Conformational investigation of the structure-activity relationship of GdFFD and its analogues on an achatin-like neuropeptide receptor of Aplysia californica involved in the feeding circuit. Phys Chem Chem Phys 20:22047-22057
Green, Daniel J; Huang, Rong-Chi; Sudlow, Leland et al. (2018) cAMP, Ca2+, pHi, and NO Regulate H-like Cation Channels That Underlie Feeding and Locomotion in the Predatory Sea Slug Pleurobranchaea californica. ACS Chem Neurosci 9:1986-1993
Rodriguez-Zas, Sandra L; Wu, Cong; Southey, Bruce R et al. (2018) Disruption of microglia histone acetylation and protein pathways in mice exhibiting inflammation-associated depression-like symptoms. Psychoneuroendocrinology 97:47-58

Showing the most recent 10 out of 227 publications