Exploiting ion mobility and high performance mass spectrometry for in-depth characterization of neuropeptides in hypoxia and pH stress

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With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Lingjun Li at the University of Wisconsin, Madison, is developing new mass spectrometry-based technology to study neuropeptide changes involved in environmental stress. Professor Li and her team focus on the study of how the structures and the concentrations of neuropeptides in a crab change under the lack of oxygen (hypoxia) or under acidic or basic conditions (pH stress). As neuropeptides represent one of the most diverse and essential classes of molecules that regulate various physiological processes, new approaches and techniques are needed to enable a more complete description of these signaling molecules and quantify their changes in response to environmental stressors. Professor Li and her group develop a set of tools based on ion-mobility mass spectrometry to separate different peptides of different size-to-charge ratios. Cataloging different peptides detected will then help to understand their roles in the brain. The funded research takes advantage of the power of analytical chemistry tools to advance neuroscience research. It provides excellent training opportunities to graduate students and undergraduate students in Professor Li's group to pursue a research career at the interface of chemistry and neuroscience. This project seeks to exploit novel use of the powerful ion mobility mass spectrometry (IM-MS) technology to address several remaining technical challenges facing neuropeptide research. Specifically, Professor Li and her team are funded to develop a novel multi-pronged approach based on IM-MS coupling to microseparations, high-performance MS, and molecular dynamic simulations for large-scale discovery, quantitation and structural elucidation of neuropeptides. They plan to improve methodologies for ion mobility assisted large-scale peptidomic analysis and accurate quantitation, its coupling to various microseparation platforms and mass spectral imaging for comprehensive neuropeptide analysis. Furthermore, they will develop a unique IM-MS based strategies to probe novel posttranslational modifications (PTMs) of neuropeptides such as D/L-peptide epimers and O-linked glycosylation. The new methodology is to improve neurochemical signaling analysis in response to hypoxia and pH stress. The technological advancements resulting from this proposal will be applicable to large-scale analysis of biochemical and peptidergic signaling in many nervous systems, including humans. The molecular insights gained from probing neurochemistry in response to stress could lead to a better understanding of neuroendocrine regulatory mechanisms involved in adapting to environmental stress, a process that is highly conserved among all organisms to maintain their survival in the face of both externally and internally generated "stimuli".