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Contents:
Catherine Fenselau Presents Saferstein Lectures
Lee Hood Visits the
Barnett Institute
William Hancock now
President-elect of HUPO
New Proteomic
Tools for Biomarker Discovery
New Instrumentation
for Metabolomic and Natural Product Analysis
Recent Papers
Catherine
Fenselau Presents Seventh Saferstein Lectures
Her first lecture, "Airborne Microorganisms
-- Detect to Protect", discussed a combination of mass
spectrometric with bioinformatics techniques to meet the
challenges of speed, reliability, ruggedness, and automatability in
detecting biological agents in buildings and battlefields. A
more technical lecture "Putting the Pieces together for
Proteomics Strategies" presented her methods for proteomic
analysis of multi-drug resistance in tumors. More Information
Photo
Gallery
Lee
Hood Visits
the Barnett Institute
Dr. Leroy Hood, President and Founder of the
Institute for Systems Biology, spent the day March 15 meeting with fellows of
the Barnett Institute. Dr. Hood spoke on the cycle of new technology enabling
new biology, the perspective of life as a
layered system of dynamic networks which integrate and modulate
information, his successful formula for finding biomarkers, and
how it extrapolates to his visionary scenario of the upcoming revolution in
medicine. More
information. Photo
Gallery
Prof.
Hancock now President-elect of US-HUPO.
At
the recent meeting of the Human Proteome Organization, Professor William Hancock,
Bradstreet Chair in Bioanalytical Chemistry at the Barnett
Institute, was elected to serve as the next president of US HUPO for a
term commencing next year.
New
Proteomic Tools for Biomarker Discovery
The Institute has, for several years, focused on
the development of new LC-MS technologies which
address priorities in biological analysis. Some recent
highlights from the Research Groups pages are:
Modification
States of Larger Proteins.
The biological activity of regulatory proteins
is controlled by posttranslational modifications
such as phosphorylation and glycosylation.
Extended Range
Protein Analysis (ERPA) combines advantages
of traditional top-down and bottom-up proteomic
analysis. 95% sequence coverage of the 180
kDa membrane protein EGFR was shown, with detailed
characterization of phosphorylation, glycosylation,
and splicing isoforms.
Targeted
Glycoprotein Analysis
Over 50% of blood proteins are glycosylated and,
in cancer, changes in glycosylation are a signpost
of progression to metastasis. Multiple Lectin
Affinity Chromatography (M-LAC) selectively extracts
glycosylated proteins from blood serum.
(see Hancock Research
for more information)
Optimizing
All Steps of the Proteomic Workflow for Different
Applications
As new advances address key limitations, the bottleneck
in proteomic analysis shifts to sample preparation
or data analysis. The Barnett's historical
strengths in separations science and its emerging
expertise in bioinformatics rapidly translates
technological advances into trial studies. Overview.
New
Instrumentation for Metabolomic and Natural
Product Analysis
NanoSplitter
LC-MS Interface
Method of coupling conventional-scale (4 mm) LC
columns to nanospray ESI-MS improves S/N 100-fold,
virtually eliminates ion suppression, and allows
99% of LC eluent to be recovered.
Micro-NMR
Microcoil NMR probes have mass limits of detection
20-fold lower than 5 mm tubes; an automated
system capable of loading 2 uL samples from
96-well plates enables ultrasensitive offline
LC-NMR.
Differential
Ion Mobility
Between the electrospray and the mass spectrometer
inlet, a drift tube with pulsed fields can preselect
ions of interest for MS, and dissociate cluster
ions to improve limits of detection 20-fold.
Recent
Papers
"Electron
Transport in the Pathway of Acetate Conversion to Methane in the
Marine Archaeon Methanosarcina acetivorans" Li, Q., Li, L.,
Rejtar,
T., Lessner, D., Karger, B.L. and Ferry, J.G., , J. of Bacteriology,
188(2), 702-710 (2006).pubmed
"High-Throughput
Axial MALDI-TOF MS Using a 2 kHz Repetition Rate Laser", Moskovets,
E., Preisler, J., Chen, H.S., Rejtar, T., Andreev, V. and Karger.
B.L., Anal. Chem., 78, 912-919 (2006).pubmed
"A New Strategy for Enhanced Characterization of Complex
Proteomic Samples Using LC-MALDI MS/MS: Exclusion of Redundant
Peptides from MS/MS Analysis in Replicate Runs" Chen, H., Rejtar,
T., Andreev, V., Moskovets, E. and Karger, B.L., Anal. Chem, 77,
7816 -7825 (2005). pubmed
"Extended
Range Proteomic Analysis (ERPA): New and Sensitive LC-MS Platform
for High Seqeucne Coverage of Complex Proteins with Extensive
Posttranslational Modifications -Comprehensive Analysis of Beta-Caesin and Epidermal Growth Factor
Receptor"Wu, S., Kim, J.,
Hancock, W.S., Karger, B.L., J. of Proteome Res., 4(4); 1155-1170,
(2005). pubmed
"Detection and Frequency Estimation of Rare Variants in
Pools of Genomic DNA from Large Populations Using Mutational
Spectrometry" Li-Sucholeiki, X., Tomita-Mitchell, A., Arnold, K.,
Glassner, B., Thompson, T., Murthy, J., Berk, L., Lange, C.,
Leong-Morgenthaler, P., MacDougall, D., Munro, J., Cannon, D.,
Mistry, T., Miller, A., Deka, C., Karger, B.L., Gillespie, K.,
Ekstrom, P., Todd, J. And Thilly, W., Mutation Research, 570,
267-280, (2005).pubmed
"Design
of an Automated Instrument with Fraction Collection for DNA Mutation
Discovery by Constant Denaturant Capillary Electrophoresis (CDCE)."Li, Q.,
Deka, C., Glassner, B., Arnold, K., Li-Sucholeiki,
X., Tomita-Mitchell, A., Thilly, W. and Karger, B.L., J. of
Separation Science, 28, 1375-1389 (2005). pubmed
"High Speed - High Resolution Monolithic Capillary LC-MALDI
MS Using an Off-line Continuous Deposition Interface for Proteomic
Analysis", Chen, H., Rejtar, T., Andreev, V., Moskovets, E. and
Karger, B.L., Anal. Chem., 77, 2323-2331 (2005).pubmed
Barnett
Institute News Archive
(links to earlier announcements and articles.)
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