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 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 neuropeptide content, and a unique capillary electrophoresis approach that allows us to sample the cytoplasm for a selected neuron or glia and characterize its metabolome. Many of these measurement capabilities are unique and not currently available elsewhere.

We use these approaches to study cell-to-cell signaling in 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 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 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 study these 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 have characterized the neuropeptides and prohormones in the sea slug, honey bee, urchin, planarian, songbird, 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.

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 and the Center for Nutrition Learning and Memory.