University of Illinois Urbana-Champaign

Characterizing neural tissues with mass spectrometry imaging via enhanced computational approaches

Zimmerman, Tyler A.

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Zimmerman_Tyler.pdf

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https://hdl.handle.net/2142/18218

Description

Title
Characterizing neural tissues with mass spectrometry imaging via enhanced computational approaches
Author(s)
Zimmerman, Tyler A.
Issue Date
2011-01-14T22:40:16Z
Director of Research (if dissertation) or Advisor (if thesis)
Sweedler, Jonathan V.
Doctoral Committee Chair(s)
Sweedler, Jonathan V.
Committee Member(s)
  • Kelleher, Neil L.
  • Rodriguez-Zas, Sandra L.
  • Wieckowski, Andrzej
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2011-01-14T22:40:16Z
Keyword(s)
  • Mass spectrometry imaging
  • neural tissue
  • nervous system
  • Aplysia californica
  • mouse pituitary
  • Planaria
  • flat worms
  • regeneration
  • computational
  • Java programming
  • software
Abstract
Neuropeptides affect the activity of the myriad of neuronal circuits in the brain. They are under tight spatial and chemical control and the dynamics of their release and catabolism directly modify neuronal network activity. Understanding neuropeptide functioning requires approaches to determine their chemical and spatial heterogeneity within neural tissue, but most imaging techniques do not provide the complete information desired. To provide chemical information, most imaging techniques used to study the nervous system require preselection and labeling of the peptides of interest; however, mass spectrometry imaging (MSI) detects analytes across a broad mass range without the need to target a specific analyte. When used with matrix-assisted laser desorption/ionization (MALDI), MSI detects analytes in the mass range of neuropeptides. MALDI MSI simultaneously provides spatial and chemical information resulting in images that plot the spatial distributions of neuropeptides over the surface of a thin slice of neural tissue. Here a variety of approaches for neuropeptide characterization are developed. Specifically, several computational approaches are combined with MALDI MSI to create improved approaches that provide spatial distributions and neuropeptide characterizations. After successfully validating these MALDI MSI protocols, the methods are applied to characterize both known and unidentified neuropeptides from neural tissues. The methods are further adapted from tissue analysis to be able to perform tandem MS (MS/MS) imaging on neuronal cultures to enable the study of network formation. In addition, MALDI MSI has been carried out over the timecourse of nervous system regeneration in planarian flatworms resulting in the discovery of two novel neuropeptides that may be involved in planarian regeneration. In addition, several bioinformatic tools are developed to predict final neuropeptide structures and associated masses that can be compared to experimental MSI data in order to make assignments of neuropeptide identities. The integration of computational approaches into the experimental design of MALDI MSI has allowed improved instrument automation and enhanced data acquisition and analysis. These tools also make the methods versatile and adaptable to new sample types.
Graduation Semester
2010-12
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http://hdl.handle.net/2142/18218
Copyright and License Information
Copyright 2010 Tyler A. Zimmerman

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