Another major proteomics initiative at the University of Kansas will
dovetail nicely with the COBRE II grant. The University received $1.5 million
from the state of Kansas as a part of a bonding authority initiative to
assemble an Analytical Proteomics Laboratory (APL), putting KU in the running
as a key center for proteomics research. Most importantly, the new equipment
will allow researchers to conduct the kind of complex analytical experiments
typical of a proteomics study.
The new lab will merge and extend activities conducted in two existing
labs, the Biochemical Research Services Laboratory (BRSL) and the Mass
Spectrometry Laboratory (MSL). APL co-directors Michail Alterman, director of
the BRSL and Todd Williams, director of the MSL, will provide complementary perspectives
on approaches to a researcher's proteomics problem. “We are very fortunate to
have research-active scientists like Todd and Michail as directors of service
research laboratories,” says George Wilson, Chair of KU's Steering Committee
on Proteomics and KU Distinguished Professor of Chemistry and Pharmaceutical
Chemistry. "They will contribute in meaningful ways to ongoing research
and to the continued development of the facilities.
The BRSL will have a primary responsibility for sample preparation, one
of the most critical steps in analytical proteomics, because if the sample is
not prepared properly, results may prove useless. Before establishment of the
Analytical Proteomics Laboratory, protein samples had to be prepared manually,
adequate for examining only small numbers of proteins, not the rising tide of
samples that new proteornics researchers will be generating.
A new automated digester will mean that the APL can become a fully
functional proteomics facility, handling increased sample throughput and rapid
tracking and analysis of samples. After protein separation by 2-D gel
electrophoresis, the resulting protein spots must be imaged and digested to
form peptides prior to analysis, which can involve hundreds to thousands of
spots. The mass information derived from the resulting peptides is used to
search databases for protein identification. Alternatively, a
multi-dimensional HPLC workstation with automated control of separation steps
and introduction to the mass spectrometer will also be available. A second HPLC
workstation will be available for researchers to develop custom separations.
The MSL will soon provide enhanced capability in MS/MS analysis, and
this will improve certainty of protein identification, mixture analysis and
post-translational modifications. A new laser capture microdissection system
will allow the lab to isolate individual cells of a specific subtype for
proteomics and genomics experiments.
Wilson says the real thrust of the new facility will be directed toward
solving biological problems and that this will require coordination between
bioanalysts and biologists, two groups of people who historically haven't
spoken the same language.
"Some proteomics problems have routine solutions; others will
involve careful consultation if meaningful results are to be obtained. There
are people who are accustomed to support facilities, such as conventional mass
spectrometry labs, where they hand in their sample on Monday and come back on
Wednesday for the result. To an increasing extent we will have to call
proteomics activities "projects," not samples. If the goal is simply
to identify the proteins in a sample, that's relatively straightforward. On the
other hand, if the goal is to find out how Much of a particular protein is
present or to look at the post-translational modifications of these
proteins, that's considerably more complicated."
The $1.5 million package that KU received stands to have a big impact on
proteomics research in the Kansas City area. Similar analytical proteomics
laboratories are already in operation at other research institutions, so KU and
the surrounding research institutions are to some extent playing catch-up.
"It is really exciting that we're going to have such research facilities
available," Wilson says. "Having them has already helped us to
attract a key faculty member in chemistry. We anticipate the same in
molecular biosciences and in the school of pharmacy as well. People who are
researching in these areas want to see that infrastructure in place."
The Kansas City Proteomics Consortium established by the Kansas City
Area Life Sciences Institute has also expressed a strong interest in supporting
the new proteomics laboratory. "We are working closely with our partners
in the Kansas City area to identify expertise and resources so that a broad
range of important biological problems can be addressed," Wilson says. •