LabAutomation 2006 - SLAS

LabAutomation2006
10:30 am Wednesday, January 25, 2006 Track 4: Informatics Room: Madera
Wyndham Palm Springs Hotel
Annette Brodte
Co-Author(s)
Genedata
Stephan Heyse
Basel, Switzerland
Michael Lindemann
Annette.Brodte@genedata.com
Oliver Duerr
Early Pharmacological Qualification of Actives by Dose-Response Series Analysis on a
Large Scale
During recent years, advances in laboratory automation and assay technologies have continuously increased the throughput in screening
campaigns. However, despite an increase in screening hits entering the drug discovery pipeline, the number of qualified lead series has not
increased substantially. This is due to frequent failures at later stages.
Parallel automated screening of 10’000s of hit compounds in panels of validation assays is a new approach for determining specificity,
selectivity, pharmacological class, and off-target effects at an early stage. Analyzing this information identifies structural classes with
appropriate pharmacology from large compound sets.
We present a case study demonstrating how large-scale validation panel screening, combined with efficient dose-response curve fitting,
is used for pharmacological classification of thousands of compounds in order to facilitate their prioritization by lead finding and medicinal
chemistry groups. This approach fails unsuitable compounds early, saving time and cost, and operates on numbers large enough to feed
the downstream pipeline despite stringent filtering with high-quality series, increasing the probability of successful discovery projects.
10:30 am Monday, January 23, 2006 Track 5: Frontiers Beyond BioPharma Room: Sierra/Ventura
Wyndham Palm Springs Hotel
Koen Bruynseels
Co-Author(s)
CropDesign NV
Gerrit Hannaert, Joris De Wolf,
Zwijnaarde, Belgium
Myriam Van Quickenborne, Chris De Wilde
koen.bruynseels@cropdesign.com
Katrien Lievens Ernst Vrancken, Nico De Wael
CropDesign
Automated Evaluation of Yield Enhancement Genes in Plants
Postulated gene functions like seed-yield-enhancement require confirmation in planta. Phenotypes need to be studied in real crops.
For hybrid-corn, classical field- testing of thousands of candidate yield-genes is virtually impossible. Rice, closely related to corn and
amenable to automated phenotypic evaluation, may function as a ‘pre-filter’. CropDesign’s TraitMill® is a high-throughput phenotype
evaluation-platform for rice. It is an assembly-line like set-up for 1) choice and design of gene-constructs, 2) vector-construction, 3) planttransformation,
4) plant-evaluation, 5) seed-evaluation, 6) statistical analysis. A sophisticated Laboratory Information Management System
(built in house) optimises the process flow between the departments. All items, from DNA-prep to seed-batch, are tagged by barcode or
transponder. LIMS functions as a tracking system for all items in TraitMill. Weekly, plants and their root systems are imaged automatically.
From the hi-res pictures software extracts parameters like plant height, green biomass, greenness-index, flowering time and root biomass.
Seeds are analysed in automated seed processing ‘towers’, directly linked to LIMS, yielding parameters like total seed-weight, kernelnumber,
filling-rate and thousand-kernel-weight. From seed images, shape parameters are automatically extracted and stored in LIMS.
Hence LIMS is also a system for data storage (12 Gb a day), data processing and reporting. Data is compiled automatically for statistical
analysis, comparing sister-populations that only differ in the absence or presence of the transgene studied. The module automatically
proposes ‘LEADs’, gene-constructs that show a significant difference between sister-populations for parameters studied.
TraitMill, and examples of LEADs it produces, will be presented from the ‘LIMS angle’.
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