The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Research in the Sweedler group focuses on cell-to-cell signaling in the central nervous system and especially on novel neurochemical pathways related to neurotransmission. Because neurotransmitters and neuromodulators are so well conserved across metazoa, we use a variety of animal models ranging from mollusks to insects to vertebrates. Using new peptidomic and metabolomic approaches—many developed by our group—we characterize these signaling molecules in samples ranging from a single cell to entire brain regions.

Why are we interested in these neuromodulatory compounds? Because of the important roles they play in behavior, learning, and memory. Cell-to-cell communication in the brain relies upon a surprising range of molecules, from gaseous molecules such as nitric oxide to classical transmitters such as glutamate, as well as unexpected molecules such as d-serine and a range of peptides. We study these in an effort to understand how networks of neurons and associated supporting cells such as glia can work together to confer emergent properties that give rise to behavior and memory. Specific queries address what molecules are present in specific cells and networks and how they change based on network activity, animal behavior or even on exposure to drugs.

Neuropeptides are perhaps the most diverse category of neuromodulators. Using a suite of mass spectrometry-based approaches, we are characterizing the neuropeptides and prohormones in the sea slug, honey bee, urcin, song bird and in several mammals. Literally hundreds of new prohormones and even more putative neuropeptides have been discovered, and the bioactivity of several of these novel neuropeptides characterized.

Complementing our peptidomics research, we also examine serotonin signaling and metabolism and nitric oxide signaling, and are currently investigating the formation and function of both d-glutamate and d-aspartate in cell-to-cell signaling. Several identified neurons use a combination of gaseous signaling, classical transmitters such as the catecholamines, and neuropeptides. We are studying the functional interactions between these three diverse classes of intercellular messengers in the same cell.

In addition to the research described above, a number of collaborative projects are undertaken through the UIUC Neuroproteomics Center on Cell-Cell Signaling, see http://neuroproteomics.scs.uiuc.edu/. For more information on the analytical development efforts involving single cell mass spectrometry, capillary-scale separations, microfabricated systems for sample introduction, and others, see: http://www.scs.uiuc.edu/chem/faculty/Jonathan_Sweedler.html