OCT 24, 2018 7:30 AM PDT

Keynote Presentation: Mass Spectrometry Approaches for the the Single Cell Chemical Characterization of the Brain

Speaker
  • Director, School of Chemical Sciences, University of Illinois at Urbana-Champaign
    Biography
      Jonathan Sweedler received his Ph.D. in Chemistry from the University of Arizona in 1988, spent several years at Stanford before moving to the University of Illinois at Urbana-Champaign in 1991 where he has been ever since. At Illinois, he is currently the James R. Eiszner Family Endowed Chair in Chemistry, the Director of the School of Chemical Sciences, and has appointments in Neuroscience, Molecular and Integrative Physiology, Bioengineering and Medicine.

      His research interests focus on developing new approaches for assaying small volume samples, and in applying these methods to study novel interactions between cells. Analytical approaches include capillary separations, micro and nanofluidics, miniaturized separations, NMR, and mass spectrometry. He and his group use these approaches to characterize cell-cell signaling molecules and unusual neurochemistry, including determining the presence, distribution and release of neurotransmitters, neuropeptides and a range of other molecules. Sweedler has created and validated neuropeptide characterization approaches including single-cell mass spectrometry, peptidomics protocols, and mass spectrometry imaging, and applied them to determine the peptidome of animal models ranging from mollusks, arthropods, nematodes, and a wide range of vertebrates (including rodents, primates and humans). They have reported more than 1000 novel peptides and 200 neuropeptide prohormones, the largest neuropeptide discovery effort ever reported. In terms of novel neurochemistry, they have discovered new neuromodulatory compounds such as unusual indoles and D-amino acids, and characterized their presence, actions and formation.

      Sweedler has published more than 500 manuscripts and presented 500 invited lectures. He is currently the Editor-in-Chief for Analytical Chemistry.

    Abstract

    In the postgenomic era, one expects the suite of chemical players in a brain region to be known and their functions uncovered. Perhaps surprisingly, many neurochemicals remain poorly characterized and for those that are known, their localization, dynamics and function are oftentimes unknown. Several approaches for assaying the chemical content within targeted brain regions and from individual brain cells are highlighted, including mass spectrometry imaging (MSI) and MS-based single cell measurements. Using these approaches, we can measure lipids, fatty acids, neurotransmitters and neuropeptides, among others. For single cell measurements, the cells of interest are scattered across a microscope slide, the exact cell positions determined via optical microscopy, and mass spectra are acquired only at the cell positions. The single cell assays allow differences in the metabolome and peptidome from supposedly homogeneous populations of cells to be explored. By obtaining information from tens of thousands of individual cells, rare cells are found and unusual neurochemicals are discovered. For select cells, follow-up capillary electrophoresis-mass spectrometry and other information rich assays can be performed. Several applications of single cell mass spectrometry are highlighted from the discovery of unusual metabolites to characterizing the both known and previously unknown neuropeptides and hormones in single cells. Our overarching goal is to uncover the complex chemical mosaic of the brain and pinpoint key cellular players involved in a range of physiological and pathological processes.

    Learning Objectives:

    1. Participants will understand why single cell measurements important.
    2. Participants will describe the importance and how cells are prepared and measured with mass spectrometry.
    3. Participants will learn about the chemical information gained from single cell mass spectrometry measurements and how it relates to cell function, health and disease.


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