New directions in kinetic high information content assays.

Kinetic high information content assays can greatly inform our understanding of cell signalling. A new generation of fluorescence and electrical detection instruments facilitates the routine use of kinetic assays within drug discovery. New biosensors enable the detection of a wide variety of signalling molecules in real-time and the potential applications of new assay approaches, such as protein fragment complementation, new biosensors, and imaging techniques, such as fluorescence lifetime imaging, broaden the range of experimental options. Greater use of kinetic, compared with snapshot, cell screening assays will enable subtle, discrete effects of compounds to be detected, aiding the interpretation of compound action and leading to a better understanding of key signalling pathways.

[1]  Hilmar Bading,et al.  Microelectrode array recordings of cultured hippocampal networks reveal a simple model for transcription and protein synthesis‐dependent plasticity , 2005, The Journal of physiology.

[2]  G Shahaf,et al.  Learning in Networks of Cortical Neurons , 2001, The Journal of Neuroscience.

[3]  S. Cavagnero,et al.  Painting protein misfolding in the cell in real time with an atomic-scale brush. , 2005, Trends in biotechnology.

[4]  James R. Johnson,et al.  Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression , 2004, Science.

[5]  J Kerby,et al.  Retinoic acid evoked-differentiation of neuroblastoma cells predominates over growth factor stimulation: an automated image capture and quantitation approach to neuritogenesis. , 2001, Analytical biochemistry.

[6]  Andreas Sewing,et al.  Fluorescence readouts in HTS: no gain without pain? , 2003, Drug discovery today.

[7]  K. W. Young,et al.  Visualizing phosphoinositide signalling in single neurons gets a green light , 2003, Trends in Neurosciences.

[8]  Derek J Trezise,et al.  IonWorks™ HT: A New High-Throughput Electrophysiology Measurement Platform , 2003, Journal of biomolecular screening.

[9]  R. Eglen.  Enzyme fragment complementation: a flexible high throughput screening assay technology. , 2002, Assay and drug development technologies.

[10]  B. Conway,et al.  The use of biosensors to study GPCR function: applications for high-content screening. , 2002, Receptors & channels.

[11]  A. Verkhratsky,et al.  Integrative Aspects of Calcium Signalling , 1998, Springer US.

[12]  M. Ferrer,et al.  Effects of cargo molecules on the cellular uptake of arginine-rich cell-penetrating peptides. , 2005, Biochimica et biophysica acta.

[13]  K. W. Young,et al.  Single Cell Analysis and Temporal Profiling of Agonist-mediated Inositol 1,4,5-Trisphosphate, Ca2+, Diacylglycerol, and Protein Kinase C Signaling using Fluorescent Biosensors* , 2005, Journal of Biological Chemistry.

[14]  M. Zaccolo,et al.  Measuring dynamic changes in cAMP using fluorescence resonance energy transfer. , 2004, Methods in molecular biology.

[15]  J. Lamerdin,et al.  Measuring drug action in the cellular context using protein-fragment complementation assays. , 2003, Assay and drug development technologies.

[16]  G. Gross,et al.  Substance identification by quantitative characterization of oscillatory activity in murine spinal cord networks on microelectrode arrays , 2004, The European journal of neuroscience.

[17]  Zoya Ignatova,et al.  Monitoring protein stability and aggregation in vivo by real-time fluorescent labeling. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Challiss,et al.  Neuronal Ca2+ stores: activation and function , 1995, Trends in Neurosciences.

[19]  Graeme Milligan,et al.  High-content assays for ligand regulation of G-protein-coupled receptors. , 2003, Drug discovery today.

[20]  Kenneth W. Young,et al.  Intracellular signalling: Receptor-specific messenger oscillations , 2001, Nature.

[21]  Peter Ramm,et al.  Image-based screening: a technology in transition. , 2005, Current opinion in biotechnology.

[22]  E. V. van Munster,et al.  Fluorescence Lifetime Imaging Microscopy (FLIM) , 2019, A Practical Guide to Optical Microscopy.

[23]  B. Strulovici,et al.  Miniaturization of Intracellular Calcium Functional Assays to 1536-Well Plate Format Using a Fluorometric Imaging Plate Reader , 2004, Journal of biomolecular screening.

[24]  T. Meyer,et al.  QT-screen: high-throughput cardiac safety pharmacology by extracellular electrophysiology on primary cardiac myocytes. , 2004, Assay and drug development technologies.

[25]  A Kusumi,et al.  Fluorescence lifetime imaging microscopy (flimscopy). Methodology development and application to studies of endosome fusion in single cells. , 1993, Biophysical journal.

[26]  Uri Alon,et al.  Dynamics of the p53-Mdm2 feedback loop in individual cells , 2004, Nature Genetics.

[27]  David S. Broomhead,et al.  Sensitivity analysis of parameters controlling oscillatory signalling in the NF-/sub K/Bpathway: the roles of IKK and I/sub K/B/sub alpha/ , 2004 .

[28]  Heribert Bohlen,et al.  Determination of electrical properties of ES cell-derived cardiomyocytes using MEAs. , 2004, Journal of electrocardiology.

[29]  Gillian R Richards,et al.  Quantitative assays of chemotaxis and chemokinesis for human neural cells. , 2004, Assay and drug development technologies.

[30]  A. Jones,et al.  Intracellular trafficking pathways and drug delivery: fluorescence imaging of living and fixed cells. , 2005, Advanced drug delivery reviews.

[31]  D. L. Taylor,et al.  High content screening applied to large-scale cell biology. , 2004, Trends in biotechnology.

[32]  H. Gerritsen,et al.  Fast fluorescence lifetime imaging of calcium in living cells. , 2004, Journal of biomedical optics.

[33]  David G Spiller,et al.  Multi-parameter analysis of the kinetics of NF-kappaB signalling and transcription in single living cells. , 2002, Journal of cell science.

[34]  Marco Peters,et al.  High content kinetic assays of neuronal signaling implemented on BD pathway HT. , 2005, Assay and drug development technologies.

[35]  G Ulrich Nienhaus,et al.  Confocal optics microscopy for biochemical and cellular high-throughput screening. , 2003, Drug discovery today.

[36]  Christian Eggeling,et al.  Highly sensitive fluorescence detection technology currently available for HTS. , 2003, Drug discovery today.

[37]  D L Taylor,et al.  Real-time molecular and cellular analysis: the new frontier of drug discovery. , 2001, Current opinion in biotechnology.

[38]  Mark H Ellisman,et al.  A FlAsH-based FRET approach to determine G protein–coupled receptor activation in living cells , 2005, Nature Methods.

[39]  Karen Allison.  The First Automated High Content Screening System , 2003 .

[40]  G. Gross,et al.  NMDA receptor-dependent periodic oscillations in cultured spinal cord networks. , 2001, Journal of neurophysiology.

[41]  S. Møller,et al.  Nuclear export inhibitors and kinase inhibitors identified using a MAPK-activated protein kinase 2 redistribution screen. , 2004, Assay and drug development technologies.

[42]  G. Bird,et al.  Techniques: high-throughput measurement of intracellular Ca(2+) -- back to basics. , 2005, Trends in pharmacological sciences.

[43]  R. Boltz,et al.  Characterization and quantitation of NF-kappaB nuclear translocation induced by interleukin-1 and tumor necrosis factor-alpha. Development and use of a high capacity fluorescence cytometric system. , 1998, The Journal of biological chemistry.

[44]  Andre Levchenko,et al.  Comment on "Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression" , 2005, Science.

[45]  Christopher C. Goodnow,et al.  Differential activation of transcription factors induced by Ca2+ response amplitude and duration , 1997, Nature.

[46]  R. Gellibolian,et al.  Homogeneous Assays for Cellular Protein Degradation Using β-Galactosidase Complementation: NF-κB/IκB Pathway Signaling , 2003 .

[47]  R Y Tsien,et al.  Specific covalent labeling of recombinant protein molecules inside live cells. , 1998, Science.

[48]  P. B. Simpson.  Ca 2+ Waves as a Form of Glial Excitability , 1998 .

[49]  Paul B Bennett,et al.  High throughput ion-channel pharmacology: planar-array-based voltage clamp. , 2003, Assay and drug development technologies.

[50]  P. French,et al.  Imaging fluorescence lifetime heterogeneity applied to GFP‐tagged MHC protein at an immunological synapse * , 2005, Journal of microscopy.

[51]  S. Møller,et al.  Identification of Akt Pathway Inhibitors Using Redistribution Screening on the FLIPR and the IN Cell 3000 Analyzer , 2005, Journal of biomolecular screening.

[52]  Conrad D. James,et al.  Extracellular recordings from patterned neuronal networks using planar microelectrode arrays , 2004, IEEE Transactions on Biomedical Engineering.

[53]  Douglas B. Kell,et al.  Response to Comment on "Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression" , 2005, Science.

[54]  Wei Zheng,et al.  Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays. , 2004, Assay and drug development technologies.

[55]  R. Pepperkok,et al.  Translocation Biosensors to Study Signal‐Specific Nucleo‐Cytoplasmic Transport, Protease Activity and Protein–Protein Interactions , 2005, Traffic.