Pushing the Frontiers of Identification and Coverage in High-Resolution Spatially-Resolved Lipidomics

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With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Julia Laskin and her group at Purdue University are developing innovative approaches to characterize biological systems using a sophisticated analytical imaging technique based on high-resolution ambient ionization mass spectrometry coupled with chemical separations including ion mobility and photochemical derivatization techniques. Specifically, methods being developed by the Laskin group are able to map the distribution of biomolecules (e.g., in tissues or cells) with high structural specificity, and with a particular focus on lipids, providing biologists with a new dimension of molecular characterization critical to understanding biochemical pathways in living systems. Graduate and undergraduate students involved in this project will be trained in a multidisciplinary and collaborative environment, which provides them with an opportunity to develop skills in instrument development, quantitative mass spectrometric imaging, data interpretation, development of new computational approaches, understanding of biological processes, photochemical reactions, and online derivatization, along with optical and shear force microscopy.This project addresses analytical challenges associated with the chemical specificity of mass spectrometry imaging experiments. In particular, the Laskin group is developing new experimental capabilities for isomer-selective ambient imaging of lipids in biological samples with high spatial resolution. Experimental strategies include ion mobility separation, online photochemical derivatization, and tandem mass spectrometry imaging, to enable unique identification and localization of isomeric species. In addition, advanced data analysis tools are being developed to enhance the resolution of ion mobility separation and to enable robust unsupervised image segmentation. By combining these tools with the quantitative high-resolution imaging capabilities of nanospray desorption electrospray ionization, the Laskin group seeks to provide detailed molecular maps of chemical gradients in biological samples with a spatial resolution better than 10 microns. The techniques being developed are expected to substantially enhance molecular coverage and enable separation and identification of isomeric and isobaric lipids observed in imaging experiments. They will be broadly applicable to studying metabolic processes in diverse biological systems including multicellular aggregates, and potentially even tissues and living cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.