Jonathan V. Sweedler / Faculty / Chemistry at Illinois

Professor Sweedler received his B.S. degree in Chemistry from the University of California at Davis in 1983 and his Ph.D. from the University of Arizona in 1989. Thereafter, he was an NSF Postdoctoral Fellow with Dr. Richard Zare and Dr. Richard Scheller at Stanford University, and joined the faculty at Illinois in 1991. He is associated with the Beckman Institute, Biotechnology Center, Neuroscience Program and Bioengineering Program. His research interests are in bioanalytical chemistry, and focus on developing new methods for assaying nanoliter volume samples, and applying these methods to study the distribution and dynamic release of neurotransmittors and neuropeptides from individual neurons. Specifically, he is investigating the roles that peptide hormones, neurotransmitters and neuromodulatory agents play in behavior, learning and memory.

Research

Research emphasis is on analytical neurochemistry. Specific technology areas include the development of analytical methods for assaying complex microenvironments, capillary electrophoresis separation methods, laser-based detection methods, MALDI sampling techniques, nanoliter volume NMR and micro/ nanofluidic sampling. The second group research theme is the application of these technologies to the study of the distribution and dynamic release of neuropeptides and classical transmitters, as well as their metabolism, in a cell-specific manner, and the investigation of the roles of neurotransmitter cotransmission in well-defined neuronal networks.

Specifically, we are developing unique capillary separation and detection systems that enable low-concentration assay of peptides from subcellular microenvironments. For example, a unique wavelength-resolved fluorescence detector provides <100-molecule detection limits with the acquisition of complete fluorescence spectra. Using this system, we detect tyrosine- or tryptophan-containing peptides, the catecholamines, indolamines, and nitric oxide synthase cofactors from a small fraction of a single cell. We pioneered the development of a high-resolution nanoliter-volume NMR probe to assay picomole amounts of mass-limited samples and couple NMR to microseparations online. Also, we are developing hybrid microfluidic/nanofluidic devices to manipulate and condition small-volume samples before analysis. Lastly, we are developing mass spectrometry protocols to measure the peptides in individual neurons and cellular processes.

Using these methods, we study the interaction of neurotransmitters and neuropeptides using the well-defined neuronal networks in the simpler nervous systems of marine invertebrates such as Aplysia californica. We have identified novel neuropeptides and neuro- hormones and documented unique processing of additional prohormones, yielding many new neuroactive peptides. Several identified neurons use a combination of gaseous signaling (NO), classical transmitters such as the catecholamines, and neuro- peptides. We are studying the functional interactions between these three diverse classes of intercellular messengers in the same cell.

This research bridges analytical chemistry and cellular neurobiology. By investigating the scaling laws of conventional analytical techniques and adapting them to the femtoliter-nanoliter range, we can assay the chemical microenvironment in and around neurons. Clearly, this work is highly interdisciplinary; we benefit from associations with the Neuro Tech and Biological Sensors Groups at the Beckman Institute, and the campus-wide Neuroscience Program.

Publications

Mass Spectrometric Imaging of Peptide Release from Neuronal Cells within Microfluidic Devices, K. Jo, M.L. Hein, L.B. Thompson, M. Zhong, R.G. Nuzzo, J.V. Sweedler, Lab Chip 7, 2007, 1454-1460.

Serotonin Catabolism in the Central and Enteric Nervous Systems of Rats upon Induction of Serotonin Syndrome, L.N. Squires, K.N. Talbot, S.S. Rubakhin, J.V. Sweedler, J. Neurochem. 103, 2007, 174-180.

Characterizing Individual Mammalian Cells using Mass Spectrometry, S.S. Rubakhin and J.V. Sweedler, Nature Protocols 8, 2007, 1987-1997.

Direct Immobilization of Fab' in Nanocapillaries for Manipulating Mass Limited Samples, B.Y. Kim, C.B. Swearingen, J.A. Ho, E.V. Romanova, P.W. Bohn, J.V. Sweedler, J. Am. Chem. Soc. 129, 2007, 7620-7626.

From Hunger to Satiety: Reconfiguration of a Feeding Network by Aplysia Neuropeptide Y. J. Jing, F.S. Vilim, C.C. Horn, V. Alexeeva, N.G. Hatcher, K. Sasaki, I. Yashina, Y. Zhurov, I. Kupfermann, J.V. Sweedler, K.R. Weiss, J. Neurosci. 27, 2007, 3490-3502.

Two Toxins from Conus striatus that Individually Induce Tetanic Paralysis, W.P. Kelley, J.R. Schulz, J. A. Jakubowski, W.F. Gilly, J.V. Sweedler, Biochemistry 45, 2006, 14212-14222.

From the Genome to the Proteome: Uncovering Peptides in the Apis Brain, A.B. Hummon, T.A. Richmond, P. Verleyen, G. Baggerman, J. Huybrechts, M.A. Ewing, E. Vierstraete, S. L. Rodriguez-Zas, L. Schoofs, G. E. Robinson, J.V. Sweedler, Science 314, 2006, 647-649.

Insights into Social Insects from the Genome of the Honey Bee Apis mellifera, The Honey Bee Genome Sequencing Consortium, Nature 443, 2006, 931-949.

Massively Parallel Sample Preparation for the MALDI MS Analyses of Tissues, E.B. Monroe, J.C. Jurchen, B.A. Koszczuk, J.L. Losh, S.S. Rubakhin, J.V. Sweedler, Anal. Chem. 78, 2006, 6826-6832.

Serotonin Catabolism and the Formation and Fate of 5-Hydroxyindole Thiazolidine Carboxylic Acid, L.N. Squires, J.A. Jakubowski, J.N. Stuart, S.S. Rubakhin, N.G. Hatcher, W.-S. Kim, K. Chen, J.C. Shih, I. Seif, J.V. Sweedler, J. Biol. Chem. 281, 2006, 13463-13470.

Bridging Neuropeptidomics and Genomics with Bioinformatics: Prediction of Mammalian Neuropeptide Prohormone Processing. A. Amare, A.B. Hummon, B.S. Southey, T. A. Zimmerman, S.L. Rodriguez-Zas, J.V. Sweedler, J. Proteome Res. 5, 2006, 1162-1167.

D-Aspartate as a Putative Cell-Cell Signaling Molecule in the Aplysia californica Central Nervous System, H. Miao, S.S. Rubakhin, C.R. Scanlan, L. Wang, J.V. Sweedler, J. Neurochem. 97, 2006, 595-606.

Vitamin E Imaging and Localization in the Neuronal Membrane, E.B. Monroe, J.C. Jurchen, J. Lee, S.S. Rubakhin, J.V. Sweedler, J. Am. Chem. Soc. 127, 2005, 12152-12153.

Imaging Mass Spectrometry: Fundamentals and Applications to Drug Discovery, S.S. Rubakhin, J.C. Jurchen, E.B. Monroe, J.V. Sweedler, Drug Discov. Today 10, 2005, 823-837.

Awards

Pittsburgh Analytical Chemistry Award
Theophilus Redwood Lecturer from the Royal Society of Chemistry
ACS Analytical Division Award in Chemical Instrumentation
The Heinrich-Emanuel Merck Prize
Fellow, American Association for the Advancement of Science
The Gill Prize in Instrumentation and Measurement Science
Benedetti-Pichler Award in Microanalysis
Beckman Fellow, Center for Advanced Study
ACS Arthur Findeis Award for Young Analytical Scientists
Camille Dreyfus Teacher-Scholar
University Scholar Award
Packard Fellow
Searle Scholar
Alfred P. Sloan Fellow
NSF Young Investigator
Camille and Henry Dreyfus New Faculty Award

Highlights

"Sensing NO in Single Cells" — Chemical Technology, October 2008 (Read the ChemTech article)

"Neuropeptides Go with the Flow" — Chemical Biology, September 2007 (Read the Chemical Biology article)

"Neurons Grow Less Dense"" — Chemical Biology, August 2007 (Read the Chemical Biologyarticle)

"Microfluidic Chambers Advance the Science of Growing Neurons" — Internetchemistry.com, August 2007 (Read the internetchemistry article) and EurekAlert, August 2007 (Read the EurekAlert article)

"PittCon Awards 2007" — Chemical & Engineering News, Vol 85, No. 12, pp. 66-67 (Read the Chemical & Engineering News article)

Sweedler Group part of The Honey Bee Sequencing Consortium — Honey Bee Genome Publication and Press Portal (Read the Press Release)

"Newly Discovered Genes, Brain Chemicals Likely Play a Role in Complex Bee Behavior" — Popular Mechanics, November 2006 (Read the Popular Mechanics article) and National Science Foundation News, October 2006 (Read the National Science Foundation News Article)