|
Contents:
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
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.
|
Prof.
Hancock
now President-elect of HUPO.
At
the recent meeting in Boston of the Human
Proteome Organization, Professor William Hancock,
Bradstreet Chair in Bioanalytical Chemistry
at the Barnett Institute, was elected to serve
as the current vice-president and next president
of HUPO, for two 2-year terms.
|
|
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
|
