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  English.dicp.cas.cn    Posted:2013-10-15
Using mass spectrometry to characterize brain neurochemistry: assaying small brain regions down to individual cells

  LocationAcademic Hall of Bio-tech Building 

  Time2013.10.18 (Friday) 2:00 p.m.

  LecturerJonathan V. Sweedler  

           Department of Chemistry, University of Illinois

  Abstract

  In the postgenomic era, one expects the suite of chemical players in a brain region to be known and their functions uncovered. However, many cell-to-cell signaling molecules remain poorly characterized and for those that are known, their localization and dynamics are oftentimes unknown. A suite of bioanalytical approaches are described that allow the investigation of individual neurons and small brain regions; these approaches include capillary scale separations coupled to mass spectrometry and direct mass spectrometric-based profiling and imaging. A key to successful measurement involves optimized tissue and cell sampling protocols. Depending on the sample being assayed and metabolites being measured, we use mechanical isolation, optical tweezers, patch pipettes, dialysis probes and microfluidics, all of which have advantages for specific sample types. Several applications of single cell microanalysis are highlighted including the discovery of unusual metabolites to characterizing the peptides in single cells. Specifically, new serotonin-related compounds, the cellular redox state, and literally hundreds of new neuropeptides have been characterized in well-defined neuronal networks, and in several cases, the functional roles of these molecules described. Imaging mass spectrometry and dynamic sampling of the extracellular environment are used for elucidating novel cell to cell signaling molecules in a range of neuronal model systems. Current technology efforts involve extending the depth of metabolome coverage and adapting these analytical approaches to higher throughput single cell assays. Our overarching goal is to uncover the complex chemical mosaic of the brain and pinpoint key cellular players in physiological and pathological processes. Several additional examples of neuropeptide and neuromodulator discovery are described across a range of metazoan life.

  Introduction

  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 Eiszner Family Professor of Chemistry, Director of the School of Chemical Science, and affiliated with the Institute of Genomic Biology and the Beckman Institute for Advanced Science and Technology. His research interests focus on developing new metabolomic and peptidomic approaches for assaying small volume samples, and in applying these methods to study novel brain neurochemistry. Besides the development of new separations, mass spectrometry and NMR tools, he uses them to characterize small molecules and neuropeptides in a range of animal models across metazoan life and in samples as small as individual neurons. Sweedler, with large international teams of biologists and technologists, has performed comprehensive interrogation of the genome, transcriptome and peptidome in Aplysia californica, Schmidtea mediterranea, Apis mellifera, Taeniopygia guttata, Strongylocentrotus purpuratus, and other models to uncover signaling peptides and pathways involved in wide range of functions and behaviors. Literally hundreds of new prohormones, a thousand novel putative neuropeptides have been discovered in these models, and the bioactivity of dozens of these novel neuropeptides characterized. This work has been published in Science, Nature, PNAS and many other journals and represents one of the most productive sets of neuropeptide discovery ever.  Acknowledging the impact of his research accomplishments, Sweedler has published more than 300 manuscripts and received more than 10000 citations to his research.  He has received numerous awards including: the ACS Analytical Division Arthur Findeis Award, the Benedetti-Pichler Award in Microanalysis, the Gill Prize in Neuroscience, the Merck Prize, the Instrumentation Award from the Analytical Division of the ACS, the Pittsburgh Analytical Chemistry Award, has been a Theophilus Redwood Lecturer from the Royal Society of Chemistry, and is a fellow of both the American Association for the Advancement of Science and the American Chemical Society. He is currently the Editor-in-Chief for Analytical Chemistry.

  ContactsGroup 1808 Xiaolin Wang (9520 )

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