October 2015 Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group
NOTE ROOM CHANGE, Mendel 115
- Topic: "Single-cell Mass Spectrometry for Cell and Developmental Biology
- Speaker:Peter Nemes, The George Washington University
- Date: Monday, October 12, 2015. 6:00 PM
- Time: Social Hour: 6:00 PM.
Talk: 7:00 PM.
- Place: Department of Chemistry, Villanova University (Mendel 115 , Mendel Hall)
Characterization of small-molecule changes during embryonic development raises a potential to deepen our understanding of basic biochemical mechanisms that coordinate healthy development. However, the success of these investigations relies on the availability of specialized analytical tools, particularly those that can measure diverse types of small molecules (metabolites) with single-cell resolution. Although high-resolution tandem mass spectrometry is the method of choice for the measurement of metabolites, typical workflows in metabolic analyses combine a large cohort, often millions, of cells to improve detection performance. Because cell pooling averages out the analytical signal among multiple cells, chemical information specific to each cell is lost in this approach. It would be transformative for cell and developmental biology to utilize mass spectrometry to detect and quantify metabolites in single embryonic cells in the developing embryo, calling for the development of high-sensitivity mass spectrometry platforms that afford compatibility with volume-limited samples.
In this talk, I will present a single-cell mass spectrometry approach we have recently developed to characterize the metabolic composition of single embryonic cells in early-stage, 16-cell embryo of the South African clawed frog (Xenopus laevis), a favorite model in cell and developmental biology. We will discuss our approach to downscale traditional metabolomic workflows in mass spectrometry to single embryonic cells, specifically how we harvest single embryonic cells from the 16-cell embryo, efficiently extract metabolites, and use a custom-built capillary electrophoresis electrospray ionization system with a commercial time-of-flight mass spectrometer to obtain qualitative and quantitative information on cell-to-cell differences in the embryo. With high-efficiency separation, accurate mass measurements, and tandem mass spectrometry, we confidently identified an appreciable set of metabolites in the metabolome of embryonic cells. Relative quantitation revealed that certain cell types exhibit metabolic heterogeneity in 16-cell Xenopus embryos. Furthermore, in functional studies we found that certain metabolites were capable to altering the cell's normal developmental fate.
We anticipate that the adaptation of mass spectrometry to single embryonic cells holds exciting, new opportunities for cell and developmental biology as well as other fields where samples are limited in volume or mass. Funding information: This research is funded by National Institutes of Health Grant R21 GM114854 and The George Washington University Department of Chemistry Start-Up Funds.
Peter Nemes, Ph.D., is an Assistant Professor of Chemistry (2013-Present) at the George Washington University, Washington DC, whence he obtained his Ph.D. in Chemistry in Professor Akos Vertes' laboratory in 2009. He completed his postdoctoral research in Bioanalytical Chemistry for Neurobiology in Professor Jonathan Sweedler's laboratory at the University of Illinois-Urbana-Champaign, IL. In 2011, he assumed a Laboratory Leader position with the US Food and Drug Administration (Silver Spring, MD), where he established a mass spectrometry facility and regulatory research program with the US Public Health Emergency Medical Countermeasures Enterprise to develop a scientific framework permitting to combat present and future threats (chemicals and biologics) to the public. Prof. Nemes' current research at the George Washington University is focused on the development of next-generation mass spectrometry platforms to assess the metabolome and proteome of volume-limited samples, specifically targeting single cells during early development of the embryo and the central nervous system. Prof. Nemes has authored and co-authored 4 book chapters and 28 peer-reviewed publications, and has presented or co-presented the results at 60+ national or international conferences. He has received the 2008 International Research Fellowship Award by the Dimitris N. Chorafas Foundation (Switzerland), the 2009 The American Institute of Chemists prize in Chemistry by The American Institute of Chemists (Washington, DC), the 2010 Science and Technology Innovation Award by Baxter Healthcare Corporation (Chicago, IL), and the 2011 Special Recognition Award by the US Food and Drug Administration. In 2015, he was appointed a Beckman Young Investigator by the Arnold and Mabel Beckman Foundation. Prof. Nemes is the co-inventor of laser ablation electrospray ionization (LAESI) mass spectrometry and holds four shared patents for this now-commercialized technology.
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