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NHLBI Proteomics CenterKeck Laboratory Description

Description of the W.M. Keck Foundation Biotechnology Resource Laboratory at Yale University

(3/20/03)

Director: Kenneth Williams, Ph.D.
Associate Director: John Flory, Ph.D.

The Keck Laboratory was founded in 1980 by Kenneth Williams, Ph.D. to bring a wide range of state-of-the-art genomic and proteomic biotechnologies within reach of hundreds of Yale and non-Yale investigators whose research programs would otherwise not benefit from the highly sophisticated and expensive instrumentation upon which biochemical and biomedical research is increasingly dependent. To maximize its positive impact, the Keck Laboratory strives to provide as many high quality services to as many investigators as possible. Although priority is always given to requests from Yale and HHMI investigators, the decision to also accept requests from scientists around the world ensures that when demand by Yale and HHMI investigators (which is highly variable) for a particular service is less than is needed to maintain maximal throughput, a backlog of requests will be available to maintain high productivity. This policy, which benefits all users of this Laboratory, minimizes operating costs and maximizes the contribution of the Keck Laboratory and of Yale University to biochemical and biomedical research. In keeping with this 23-year guiding philosophy, the majority of analyses and syntheses are provided on a non-collaborative basis - as it simply would not be feasible for this unit to collaborate simultaneously with even a small fraction of the >1,100 investigators who utilize its services annually. Throughout its history, the Keck Laboratory has been close to self-supporting in that it has recovered 80% of its salary, supply, and instrumentation costs from service charges. In addition, 18% of its historical budget has derived from grant and contract support with <2% of its support deriving from Yale University, YSM and individual YSM departments. With 45 full time staff, including 12 with Ph.D. and 6 with M.S. level degrees, and >75 major instrument systems purchased at a cost of >$7 million dollars, the Keck Laboratory is one of the largest academic biotechnology resource laboratories of its kind in the world.

The 12 individual Resources that are the Keck Laboratory provide a wide variety of genomic and proteomic syntheses and analyses that include DNA microarray and chip technology, oligo and peptide synthesis, DNA and protein sequencing, biophysical analysis of proteins and other biopolymers (including size exclusion HPLC/laser light scattering and stopped flow fluorescence/absorbance), biostatistical analyses, and mass spectrometry. DNA microarray technology is one of the newer genomic technologies offered and the Keck Lab now has available 1" x 3" glass slide microarrays that allow the relative level of expression of 27,000 Arabidopsis, 15,000 mouse, 5,000 rat or 17,000 human genes and ESTs to be interrogated in parallel in a single experiment. Indicative of the increasing trend towards higher throughput technologies, the Keck Lab opened a highly automated protein identification service that starts with investigators submitting protein-containing, polyacrylamide gel bands or spots in 96 well plates. In 2002 the Keck Lab also opened a Single Nucleotide Polymorphism (SNP) Genotyping Resource with a maximum throughput of >20,000 SNP genotypes/day. Mass spectrometric-based technologies being developed include one that is directed at finding naturally occurring peptide/protein "biomarkers" in serum and other biological samples to hopefully allow a wide range of human diseases to be more accurately diagnosed (particularly at an earlier stage than is now possible), classified and understood; and both 2D gel and mass spectrometric-based protein profiling services to enable "genome level" comparison of the relative level of expression of thousands of proteins in whole cell extracts. This latter effort will be substantially strengthened by the recent awarding of a $1.4 million dollar NIH High End Instrumentation Grant to the Keck Laboratory to fund the purchase of an FT-ICR mass spectrometer and by the recent award of an $18 million NIH contract to establish the Yale/NHLBI Proteomics Center which will be strongly supported by the Keck Lab.

As suggested by the number of services it provides, the Keck Lab is making an important contribution to biological and biomedical research which extends far beyond Yale University. In calendar year 2002 the Keck Lab provided 215,383 genomic and proteomic analyses and syntheses to 422 Yale and 692 non-Yale investigators at more than 350 institutions in 20 countries. To enable the Keck Lab to continue to expand to meet the 40% average annual increase (since 1990) in demand for services, the Yale School of Medicine is providing an additional 4,500 ft2 of space which will bring the total Keck Lab space to approximately 20,000 ft2. To help its users take maximum advantage of its Resources, the Keck web pages provide extensive background information on the biotechnologies it offers and on interpreting the resulting data. That this effort is succeeding is suggested by the web log which indicates that in January, 2003 the Keck web pages received 750,000 requests from 5,600 distinct hosts.

As judged by extensive use of the Keck Laboratory by non-Yale investigators and by comments like the following by the NIH Study Panel that reviewed a recent Shared Instrumentation Grant (RR151837 in 2001), the Keck Laboratory provides a very high level of service to its users and is dedicated to continuing to do so far into the future:

"This is an outstanding proposal from a premiere core laboratory at Yale." "The Keck Biotechnology Resource Laboratory is arguably one of the best facilities of its kind in the nation in terms of support and expertise. The large number of researchers who annually make use of this facility, both from the Yale campus and nationwide, is testament to the significance of the facility for crucial support of biomedical and biotechnology research."

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Last modified: 27-Mar-2006 (GB)