Recent progress in single-cell and spatial proteomics

Recent progress in single-cell and spatial proteomics

Apr 14, 2023 - 3:20 PM
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Ryan Kelly

Ryan Kelly, Ph.D. Associate Professor, Department of Chemistry and Biochemistry, Brigham Young University

Host: Dr. Lee

Biological tissues are highly heterogeneous, consisting of a variety of cell types, states and subpopulations, and understanding heterogeneity at the single cell level is of great interest for biomedical research. We have developed a platform termed nanoPOTS (Nanodroplet Processing in One pot for Trace Samples) to minimize sample losses normally incurred during sample processing. In combination ultra-low-flow separations and latest-generation mass spectrometry instrumentation, we now achieve in-depth proteome coverage for low-input samples including single cells. To date, we can quantify >3000 proteins from single mammalian cells and achieve similar coverage for frozen and FFPE tissue squares as small as 50 µm. We will describe advances in cell isolation, sample preparation, ultrasensitive separations, MS acquisition and data analysis that have made this possible, as well as efforts to minimize or eliminate the need for custom instrumentation for such analyses. Finally, prospects for further dramatically improving the measurement throughput, depth of proteome coverage and quantitative accuracy for single-cell and other low-input proteomics studies will be discussed.

Ryan Kelly is an Associate Professor in the Department of Chemistry and Biochemistry at Brigham Young University (BYU). He received his Ph.D. in analytical chemistry from BYU in 2005 and spent the next 13 years as a postdoc and then staff scientist at Pacific Northwest National Laboratory (PNNL). He joined the faculty of BYU in 2018.

A central theme of Dr. Kelly’s research has been the development of new technological solutions for ultrasensitive biochemical analyses. His recent efforts have focused on single-cell proteomics and spatial proteomics. This has involved tailoring sample preparation for small samples by developing the nanoPOTS (Nanodroplet Processing in One pot for Trace Samples) workflow, as well as optimizing separations, ionization and mass spectrometry acquisition for low-input samples. He continues to focus on improving sensitivity, throughput and quantification for single-cell proteomics and other sample-limited analyses.

Dr. Kelly has authored or coauthored more than 100 publications and is a named inventor on several patents that have been licensed and commercialized by companies including Bruker, Cellenion and his own recent startup, MicrOmics Technologies. His work has been recognized with several awards including two R&D 100 awards, the Georges Guiochon HPLC Faculty Fellowship and the HTC Innovation Award.