Creating an automated assay team with multiple skills that can support diverse screening responsibilities is a key challenge for drug discovery research sites. Development of ultra high throughput screening (uHTS) screens, development of lead identification and lead optimization assays within medicinal chemistry supported projects, and automation and miniaturization of assays are best performed by a dedicated team of varying backgrounds, experience, and skill sets. This article discusses how integration with therapeutic franchises, regular communication processes, and formal and informal cross-training facilitate the establishment of a streamlined and efficient model at our site for supporting multiple projects at relatively modest financial outlay and recruitment levels.
SimpsonP. B.WoollacottA. J.PillaiG. V.MaubachK. A.HadinghamK. L.MartinK.ChoudhuryH. I.SeabrookG. R.Pharmacology of recombinant human GABAA receptor subtypes measured using a novel pH-based high-throughput functional efficacy assay. J. Neurosci. Methods.2000, 99, 91–100.
2.
WoollacottA. J.SimpsonP. B.High throughput fluorescence assays for the measurement of mitochondrial activity in intact human neuroblastoma cells. J. Biomol. Screen.2001, 6, 407–14.
3.
AdkinsC. E.PillaiG. V.KerbyJ.BonnertT. P.HaldonC.McKernanR. M.GonzalezJ.OadesK.WhitingP. J.SimpsonP. B.α4β3δ GABAA receptors characterized by fluorescence resonance energy transfer-derived measurements of membrane potential. J. Biol. Chem.2001, 276, 38934–9.
4.
ZhengW.CarrollS. S.IngleseJ.GravesR.HowellsL.StruloviciB.Miniaturization of a hepatitis C virus RNA polymerase assay using a −102 degrees C cooled CCD camera-based imaging systemAnal. Biochem.2001, 290, 214–20.
5.
KornienkoO.LacsonR.KunapuliP.SchneeweisJ.HoffmanI.SmithT.AlbertsM.IngleseJ.StruloviciB.Miniaturization of whole live cell-based GPCR assays using microdispensing and detection systems. J. Biomol. Screen.2004, 9, 186–95.
6.
SimpsonP. B.BachaJ. I.PalfreymanE. L.WoollacottA. J.McKernanR. M.KerbyJ.Retinoic acid-evoked differentiation of neuroblastoma cells predominates over growth factor stimulation: An automated image capture and quantitation approach to neuritogenesis. Anal. Biochem.2001, 298, 163–9.
7.
RichardsG. R.MillardR. M.LeveridgeM.KerbyJ. E.SimpsonP. B.Quantitative assays of chemotaxis and chemokinesis for human neural cells. Assay Drug Dev. Technol.2004, 2, 465–72.
8.
RichardsG. R.KerbyJ. E.ChanG. K. Y.SimpsonP. B.Automated cell plating and sample treatments for fixed cells in high content assays. In High Content Screening: A Powerful Approach to Systems Cell Biology and Drug DiscoveryTaylorD. L.GiulianoK. A.; Eds.; Humana Press, in press.
9.
ChanG. K. Y.RichardsG. R.PetersM.SimpsonP. B.High content kinetic assays of neuronal signalling implemented on BD Pathway HT. Assay Drug Dev. Technol2005, 3, 623–36.
10.
RichardsG. R.KerbyJ. E.ChanG. K. Y.SimpsonP. B.Automated cell plating and sample treatments for fixed cells in high content assays. Methods Mol. Biol. Vol. 356. In High Content Screening: A powerful approach to systems cell biology and drug discovery;GiulianoK. A.TaylorD. L.HaskinJ.; Eds., Totowa NJ: Humana Press, Inc.; 2006;.
11.
SimpsonP. B.WoollacottA. J.HillR. G.SeabrookG. R.Functional characterization of bradykinin analogues on Chinese Hamster Ovary cells expressing recombinant human B1 and B2 bradykinin receptors. Eur. J. Pharmacol.2000, 392, 1–9.
12.
SmithA. J.OxleyB.MalpasS.PillaiG. V.SimpsonP. B.Compounds exhibiting selective efficacy for different β subunits of human recombinant GABAA receptors. J. Pharmacol. Exp. Ther.2004, 311, 611–9.
13.
KunapuliP.RansomR.MurphyK. L.PettiboneD.KerbyJ.GrimwoodS.ZuckP.HodderP.LacsonR.HoffmanI.IngleseJ.StruloviciB.Development of an intact cell reporter gene beta-lacta-mase assay for G protein-coupled receptors for high-throughput screening. Anal. Biochem.2003, 314, 16–29.
14.
MooreK.ChanG. K. Y.LeechC.AllisonK.WarringtonK.WhitesideM.SimpsonP. B.A high specification dual arm robot screening platform designed for flexible operation. Poster at Society for Bio-molecular Screening 11th Annual Conference and Exhibition, Geneva, Switzerland, Sep 2005.
15.
HodderP.MullR.CassadayJ.BerryK.StruloviciB.Miniaturization of intracellular calcium functional assays to 1536-well plate format using a fluorometric imaging plate reader. J. Biomol. Screen.2004, 9, 417–26.
16.
MooreK.W.ChandlerG.WhalleyP.GannonD.SimpsonP.B.Efficient sample logistics—from the medicinal chemist's bench to the assay plate and beyondJ. Assoc. Lab. Autom. in press.
