4th Annual New England Users' Meeting
August 4, 2008
Many thanks to all who attended our 4th annual New England users meeting. And a special thank you to the speakers who so generously shared their research. Below is a list of presentations, and if available, a link to the presentation in .pdf format. If a presentation is not available, please contact the presenter directly.
- A Successful Cross-Zone Evaluation of CellKey
Karen Cook, Pfizer, Inc.
- Cells, Electrodes and Faraday!
Sam Varma, Pfizer, Inc
- Label-free approach to Ion Channels, a New Perspective
Richard Kondo, Ph.D., Molecular Devices
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Label-free based measurement is a breakthrough technology for doing cell-based assay’s for drug discovery screens. It has permitted the routine measurement of the pharmacology of ligand interaction with endogenous receptors and in primary cells. We have investigated to what extent the CellKey platform can be used to screen ligand-gated ion channels. I shall provide data regarding a CellKey assay designed to measure the pharmacology of activation and inhibition of GABA(A) chloride channels. The EC50’s and IC50’s of reference compounds for activation and inhibition of the GABA(A) channels are similar to reported literature values as determined by radioligand binding and colometric cell-based assays. Therefore, the CellKey is providing a new technology for measuring ligand-gated ion channels, especially in heretofore challenging targets such as primary cells.
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The CellKeyTM System Product Family: Enabling Technology for Drug Discovery
Debra Gallant, Molecular Devices
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Presentation provides an update on how the CellKey™ System products are being used as an enabling technology by current users. Cases studies are shown demonstrating the use of the technology for measurement of intractable GPCR targets and how use of the CellKey™ System is providing a simple means to develop assays typically difficult if not impossible to develop in other formats. Additionally use of the system for focused screening and the introduction of the CellKey™384 System for high throughput label-free cell based screening are discussed.
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Screening for screening agents: Discovery of fluorescent small-molecule probes of muscle differentiation
Bridget K. Wagner, Ph.D., The Broad Institute of Harvard and MIT
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A small molecule capable of distinguishing the distinct states resulting from cellular differentiation would be of enormous value, for example, in efforts aimed at regenerative medicine. We screened a collection of fluorescent small molecules for the ability to distinguish the differentiated state of a mouse skeletal muscle cell tine. High-throughput fluorescence-based screening of C2C12 rnyoblasts and myotubes resulted in the identification of six compounds with the desired selectivity, which was confirmed by high-content screening in the same cell states. The compound that resulted in the greatest fluorescence intensity difference between the cell states was used as the screening agent in a pilot screen of 84 kinase inhibitors, each present in four doses, for inhibition of myogenesis. Of the kinase inhibitors 17 resulted in reduction of fluorescence at one or more concentrations; among the "hits" included known inhibitors of myogenesis, confirming that this compound is capable of detecting the differentiated myotube state. We suggest that the strategy of screening for screening agents reported here may be extended more broadly in the future.
- A High-Speed Time-Lapse Video Platform for Analyzing Effects of GPCR and Ion Channel Modulators on Cardiomyocyte Contraction
Mei Zhang, M.D., Ph.D., Synta Pharmaceuticals
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To predict in vivo drug effects on the cardiovascular system, we introduce a unique and sensitive high speed time-lapse imaging platform, and demonstrate quantitative phase-contrast imaging analysis of the effects of multiple GPCR and ion channel modulators on cultured, live, primary rat cardiomyocytes. Video pairs will be presented of the same cells, captured during sequential compound treatments.
- Laser Scanning Cytometry with the IsoCyte
Neil Bristol, Blueshift Technologies
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