May Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group
Manufacturer's Night, includes dinner and corporate posters. Please RSVP by May 7.
ACS Philadelphia Section,
- Topic: "Accurate, Sensitive and Comprehensive Characterization of Biological Molecules by Electrospray Ionization FT-ICR Mass Spectrometry"
- Speaker: David Muddiman, Professor of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota.
- Date: Monday, May 13, 2001. 6:00 PM
- Time: 6:00 Buffet Dinner hosted by
7:00 Socializing/Vendors presentations
- RSVP for the Dinner to Scott Van Bramer by May 8.
- Place: Merck, West Point, 37 Auditorium
DNA sequence determination has become a central theme of genetic research. The completion of the first rough draft of the human genome just prior to the 50th anniversary of Watson and Crick's discovery of the molecular structure of DNA, was accomplished using conventional techniques. However, characterization of sequence variations in the "re-sequencing era" will demand more rapid and accurate methodologies than those that currently exist. Genetic mapping will continue to be an important functional analysis tool well into the next century and electrospray ionization mass spectrometry offers the potential to be a new strategy for such purposes. It has already become abundantly clear that the availability of raw sequence data on the entire human genome will provide little insight into the location and function of genes that are related to human health and disease. To achieve this goal, disease genes must be mapped to their cognate sequences. The increasing availability of raw data on expressed sequence has made it possible to contemplate radical new mapping strategies which will depend critically upon the sequences of samples from large number of individuals with phenotypically similar diseases, potentially caused by heterogeneous disease loci. This part of the presentation will detail our efforts at developing ESI-MS for the rapid and accurate genotyping of short tandem repeats, including those with microheterogeneity within the repeating sequence. This research is also expected to have a significant impact in human identification in cases of disasters, paternity suits, and forensic science with future endeavors directed toward HLA typing.
The human genome is extremely static (fortunately) compared to the transcriptome and proteome and thus, knowledge of which proteins are expressed under a given set of circumstances is invaluable. However, our research group is interested in developing electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry, which can provide sub parts-per-million mass accuracy, multi-stage mass spectrometry capabilities, ultra-high mass resolution over a wide m/z range and the ability to manipulate ion populations as a quantitative strategy to monitor gene expression at the translational level. Recent reports have clearly, but not surprisingly, reported that mRNA levels do not correlate well with their cognate protein levels. This part of the presentation will focus on our efforts, using relatively simple systems, at understanding the role in which ESI-FTICR could play in quantitative proteomics, where quantification of relative molecular ion signals is critical but currently not well understood. Furthermore, this part of the presentation will present a rapid (~4 seconds), sensitive (single acquisition of proteolytic digests from 0.5 nM solutions) and selective (phosphopeptides are detected with 3 times the sensitivity of their unmodified sequence) method for phosphopeptide mapping which utilizes infrared multi-photon dissociation.
David C. Muddiman is currently a Professor of Biochemistry and Molecular Biology and the Director of Developmental Mass Spectrometry for the Study of Biological Complexity at the Mayo Clinic and Foundation in Rochester, Minnesota. Prior to moving his research group to the Mayo Clinic, David C. Muddiman was an Associate Professor of Chemistry at Virginia Commonwealth University where he began his academic career in 1997 with an adjunct appointment in the Department of Biochemistry & Molecular Biophysics where he is also a member of the Massey Cancer Center. David was born in Long Beach, CA in 1967 but spent most of his formidable years in a small town in Pennsylvania. David received his B.S. in chemistry from Gannon University (Erie, PA) in 1990 and his Ph.D. in Analytical Chemistry from the University of Pittsburgh in 1995 under the auspices of David M. Hercules. He then was a Postdoctoral Fellow at Pacific Northwest National Laboratory in the Environmental Molecular Sciences Laboratory working with Richard D. Smith from 1995-1997. David's research focuses on the development of high performance mass spectrometry to interrogate gaseous ions for DNA polymorphism determination, drug-DNA interactions, DNA methylation, and protein quantification and post-translational modifications. He has presented over 45 invited lectures, given over 45 presentations at national meetings, has published over 45 peer-reviewed papers and is the recipient of the 1999 American Society for Mass Spectrometry Research Award.
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