Jonathan V. Sweedler

We develop a variety of analytical measurement methodologies, including microfluidic/nanofluidic sampling, capillary electrophoresis separations, and mass spectrometry characterization. These technologies combine to form metabolomics and peptidomics workflows, with much of our efforts directed toward scaling these methods to the nanoliter and smaller volume levels. We are currently developing a range of mass spectrometry imaging approaches that allow thousands of individual cells to be characterized for their lipid, metabolite, and peptide contents. Many of these measurement capabilities are unique and not currently available elsewhere.

We use these approaches to study cell-to-cell signaling in a broad range of systems, including the central nervous system to uncover novel neurochemical pathways. Because neurotransmitters and neuromodulators are so well conserved across the entire animal kingdom, we work with a wide variety of animal models, from mollusks to insects to vertebrates. We use new peptidomic and metabolomic approaches—many developed by us—to characterize these signaling molecules from individual cells to entire brain regions.

Why are we interested in these compounds? Because of the important roles they play in behavior, learning, and memory. Cell-to-cell communication in the brain relies upon a surprising array of molecules, from gaseous molecules (e.g., nitric oxide) to classical transmitters (e.g., glutamate), as well as unexpected molecules (e.g., d-serine), and a range of peptides. We have discovered literally hundreds of new prohormones and even more putative neuropeptides, and the bioactivity of several of these novel neuropeptides characterized.  We use the same approaches to study cell-cell signaling in microbial systems, including studies on the microbe / gut / brain axis in mammals.

One research area is 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.

In addition to the research described above, a number of collaborative projects are undertaken through the UIUC Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling.