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3:30 pm
Chemistry Building, Room 1402

Pioneering Ultrahigh-Sensitive Mass Spectrometry: Single-cell Discoveries in Cell and Neurodevelopmental Biology

Speaker: Dr. Peter Nemes, UMCP


Abstract: Knowledge of all the types of molecules that are produced in cells as they establish different tissues and organs is key to understanding normal development and function and design efficient therapeutics. Even today, after the sequencing of entire genomes, there is limited information on how molecules downstream, specifically proteins and metabolites contribute to cell processes. The limitation has been a lack of sufficiently sensitive high-resolution mass spectrometry (HRMS) technologies that can measure these biomolecules with scalability in space and time and compatibility with in vivo conditions, a prerequisite for functional biological studies. In this presentation, I will discuss ultrahigh-sensitivity HRMS technologies that my laboratory has pioneered to enable single-cell measurements in situ and also in vivo. Our custom-built capillary electrophoresis and electrospray ionization interfaces enabled a record 30 zmol (~18,000 copies) lower limit of detection and a broad 6-log-order linear dynamic concentration range for quantification. These analytical performance metrics allowed us to embark on a systematic exploration of molecular differences between specific, identified cells in live embryos of X. laevis (frog) and zebrafish and identified neurons in the mouse central nervous system. Our quantitative data on thousands of different proteins and hundreds of different metabolites revealed previously unknown molecular heterogeneity between cells and neurons in these systems. These insights in turn allowed us to design hypothesis-driven studies to test the biological significance of the dysregulated molecules, leading to multiple discoveries along the way, including: (i) molecules that can alter normal cell fate decisions; (ii) long-range small-molecular gradients in the embryo; (iii) signaling between neighboring embryonic cells; (iv) small-molecular patterning of the embryonic body plan; (v) early metabolic impacts on the cognitive-visual performance. As we learn more about molecules, our biological experiments call for enhancements in analytical performance, thus mutually strengthening chemistry and biology forward to help better understand the cell, the functional building block of life.


Special Seminar

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