|An Ultra-High Throughput Approach to High Content Screening in 1536-Well Format|
Yan Wang, Robert L. Davis and Wayne Bowen
The Acumen Explorer combines the object-recognition capabilities of image-based systems with read speeds similar to that of bulk readers. Here, we demonstrate the powerful integration of an Acumen Explorer with the Kalypsys® Integrated Screening System, with capability to screen > 300,000 wells per day of high content data.
|High Throughput Cell Cycle Analysis using Microplate Cytometry|
Tristan Cope and Wayne Bowen
To improve screening efficiency, we have developed a cell cycle analysis method that uses an Acumen Explorer fluorescence microplate cytometer to measure the DNA content of propidium iodide stained fixed cells in microplates. We demonstrate that paclitaxel and vinblastine arrested CHO cells in the expected phase of the cell cycle.
|Detecting the FRET Response of the GeneBLAzer® Cell Line D1 CRE-bla CHO-K1 to Agonists and Antagonists using Microplate Cytometry|
Christopher Lupton, Randy Hoffman, Paul Wylie and Wayne Bowen
The GeneBLAzer® CHO.K1-D1 cell line (Invitrogen) stably expresses both the ß-lactamase gene downstream of the cAMP response element (CRE) and the dopamine D1 receptor. Stimulation of the cells with dopamine D1 receptor agonists, results in transcriptional activation of the ß-lactamase gene through CRE. A FRET-enabled substrate (CCF4-AM) fluoresces green, in the absence of ß- lactamase reporter activity, and blue when cleaved.
|Communicating Drug Discovery Data Efficiently and Effectively|
Jonathan Davies and Andrew Lemon
In this poster, we present IDBS’ ActivityBase™ - a single, integrated framework that brings together biological and chemical information. The software integrates with Oracle®, the industry standard relational database and familiar Microsoft® applications such as Word and Excel. With all discovery data in one system, the communication of information between scientists is simplified - enabling better, faster decisions and the need for IT support to integrate disparate systems is eliminated.
|A new High Content Screening Paradigm: Combination of Image Analysis Software and Microplate Cytometry|
Sarah Payne, Paul Wylie, Simon Carter and Wayne Bowen
Researchers are under increasing pressure to perform high content cell-based assays at throughputs compatible with primary screening. Where throughput is not an issue, microscope-based CCD imagers have predominated within the high content field, due to the breadth of biological assays that can be addressed by image analysis techniques. However, they have limited utility for screening due to their low throughput, limited field of view and generation of terabytes of image data.
|Cloe Screen MDR1-MDCK: A Predictive Model of Drug Permeability|
David Turner, Boris Pufong, Susan Hinchliffe, Gayle Corkill, Deborah Slamon, Peter Dykstra, Helen Gill, Clive Dilworth and Darwin Cheney
A MDR1-MDCK permeability screen for assessing the membrane permeability properties of early drug discovery compounds has been developed. This study measured the bi-directional transport of compounds with a range of permeabilities across MDR1-MDCK monolayers. Drug concentrations were analysed by LC-MS/MS, from which apparent permeability values in apical-basolateral and basolateral-apical directions and asymmetry index were calculated.
|Study Management in Late Stage Discovery and Preclinical Research|
Glyn Williams and Paul Denny-Gouldson
Organizations need to streamline their operations by managing the entire lifecycle of an experiment - from design to final publication of data. Organizations require the full benefits of IP protection, with the ability to access a solution for data capture, reduction, statistical analysis, charting and data curation. Researchers want a familiar notebook interface that they can use to create and manage study reports and publish data to corporate warehouses and document systems.
|A Software-Aided Approach to Reducing the Synthetic Burdens of Lead Structure Optimization|
Sanjivanjit K. Bhal, Karim Kassam and Ed Kolovanov
Following the identification of a lead compound, the usual next step is optimization of that lead via slight structural modifications to improve or retain potency while simultaneously minimizing liabilities. Achieving this balance of required properties is a significant challenge. ACD/Structure Design Suite is a software tool that significantly helps the medicinal compounds that are expected to produce analogs with improved selected physicochemical properties.
|Gene Experssion-based Prediction and Mechanistic Assessment of Non-Genotoxic Chemical-Induced Hepatocarcinogenicity |
Mark R. Fielden and Richard J. Brennan
To facilitate both prediction and mechanism-based assessment of human cancer risk, a liver gene expression signature was derived from short term experiments in the rat to predict non-genotoxic hepatocarcinogenicity. The signature was shown to classify 47 independent chemicals with 85% accuracy, much greater than other putative early biomarkers.