Assay Development
This Initiative is one component of the MLP and constitutes a major NIH effort to broaden access to rapid assay technologies. This program will fund the development and adaptation of biological assays for use in automated high throughput molecular screening (HTS). It is intended that this Initiative promote the development of automated screening projects that can be submitted to the MLPCN. High throughput molecular screening (HTS) is the automated, simultaneous testing of thousands of distinct chemical compounds in models of biological mechanisms. Active compounds identified through HTS can provide the starting point in the design of powerful research tools that allow pharmacological probing of basic biological mechanisms, and which can be used to establish the role of a molecular target in a disease process, or, its ability to alter the metabolism or toxicity of a therapeutic. The immense potential of HTS to impact our understanding of biological mechanisms is largely untapped because access to automated screening facilities and large compound libraries is limited in academic, government and non-profit research sectors. Many in vitro biological models are currently used to study biological pathways, the effects of genetic perturbations and to establish a disease association. These can be adapted to high throughput formats for the purpose of screening large collections of biologically active compounds. There are a number of characteristics that make an assay suitable for high throughput approaches. The assay must be robust, reproducible and have a readout that is amenable to automated analysis. In addition, it must be possible to miniaturize the assay, for example; to a 96-well plate (or higher density) format or flow-cytometric approach. Further, the assay protocol should be simple enough for automated handling. A broad range of models share many of these features, including; biochemical assays, cellular models and certain model organisms such as yeast or C. elegans. This initiative will support the development of innovative assays for use in both basic research and in therapeutics development programs, with an emphasis on novelty of assay approach and/or novel targets and mechanisms.
Funding Opportunities
For information about the current Assay Development PAR (PAR-08-024), please click on the embedded link or contact:Mark Scheideler, Ph.D.(National Institute of Neurological Disorders and Stroke)
Data Sharing
As the objectives of each Assay Development for HTS may be somewhat unique, so may the particular data sharing plans associated with them. Therefore, interested investigators are strongly encouraged to review the data sharing plans of each RFA in concert with the specific aims of the particular Announcement.
For information about the previous RFA’s data sharing plan, see “Section V. of Assay Development for HTS.
Funded Research
To download details on the Assay Development Funded Projects and links to abstracts and publications, click here.
The table below contain a brief summary of the document.
Assay Development Funded Research
| PI name | Title | Publications |
|---|---|---|
| Bezprozvanny, Ilya B | Screen for blockers of a CaV2.2-Mint-PDZ1 association | |
| Burgess, Richard R | LRET-based HT Screening for Inhibitors of Transcription | 15950166 |
| Burns, Charles G | HTS assay for zebrafish embryonic heart function | 16408054 |
| Chiosis, Gabriela | Development of HTS assays probing Hsp90 inhibition | 16797988, 16392823, 15828828 |
| Chung, Raymond T | Chemical Genetics to Identify Cellular Regulators of HCV | 17241881 |
| Clardy, Jon C | High-throughput Screens for P. falciparum Malaria | 17116676 |
| Conn, P Jeffrey | Development of a High Throughput Assay for Allosteric Potentiator of GluR | 16135701 |
| David, Sunil A | Novel High-throghput Assay for Angiogenesis Inhibitors | 15755654, 16454684, 15801849, 16398551, 15713373, 15578935 |
| Fenton, Robert G | High-throughput screen for inhibitors of Mcl-1 | |
| Frank, David A | High Throughput Screening for Modulators of STAT5 | 16840779, 16819511, 15498775 |
| Goldfarb, David S | Molecular Screen for Lifespan Extension in Yeast | 15489200 |
| Harsay, Edina | Identifying compounds that target post-Golgi secretion | |
| Jayaraman, Vasanthi | High throughout screening assay for glutamate receptors | 17260963, 16408071 |
| Kieff, Elliott D. | Screening of Epstein Barr Virus Replication | |
| Kirken, Robert A | Screening for small molecule inhibitors of Stat5 | |
| Kutsch, Olaf | A GFP Based HTS Assay for HIV-1 Tat Inhibitors | 16831859, 17477827, 16454046 |
| Lithgow, Gordon | C. elegans, Aging and High Throughput Screening | 16741121, 16626392, 16626392 |
| Lu, Yiling | Tissue Lysate Arrays for Molecular Screening | 17041095 |
| Manion, Michael K | Methods to identify BCL-2 "gain of function" inhibitors | |
| Morisseau, Christopher | Cyanohydrin based fluorescent substrates of sEH | 16729954, 16359636, 16142916, 15963942 |
| Perrimon, Norbert | High-throughput screen for host factors in Listeria infection | 17086199, 16844385, 16020694, 16020693, 15644175 |
| Rosenfeld, Steven S | Development of High Throughput Screening Assays to Targ* | |
| Thacher, Scott M | Small Molecular Screen for Thymocyte Drug Target | |
| Tortorella, Domenico | Luminescent assay to identify ER dislocation inhibitors | |
| Tse-Dinh, Yuk-Ching | Development of a HTS system in E. coli for topoisomeras targets | 17346206, 17317696, 16159875 |
| Waldman, Todd A | Isogenic Cell-Based Screens for Cancer: Targeting PTEN | |
| Wilson, Robert B | High throughput screen for cyclin D1 inhibitors | |
| Wright, Kenneth L | High Throughput H3-K9 Methyltransferase Inhibitor Screen | |
| Xie, Simon X | HTS Assay for Ca 3 T-type Channels Using FLIPR | 17477828, 16627567 |
| Yaffe, Michael B | High-Throughput Assay Design for Polo Kinase Inhibitors | |
| Bacher, Adelbert | HTS on Riboflavin and Terpene Biosynthetic Enzymes | 17400171, 17348709, 17081012 |
| Caffrey, Michael S | High Throughput Screening of HIV Entry Inhibitors | |
| Cartegni, Luca | Development of HTS Assays to Identify Specific Alternative Splicing Modulators | |
| Christensen, Kenneth A | Assay for Molecules that Inhibit Anthrax Intoxication and Pathological Angiogenes | |
| Clardy, Jon C | Phenotypic-based High Throughput Screens for Plasmodium Falciparum Malaria | 17116676 |
| Crawford, Brett E | Cell-Based Screen for Inhibitors of Mucin-Type O-Linked Glycans | |
| Cuevas, Bruce D | MEKK2/3-MEK5 Protein Interaction/Activation/ERK5 Pathway | |
| Delpire, Eric J | Identification of Novel Modulators of CL-dependent Transport Processes via HTS | 17581962 & 17493914 |
| Devi, Lakshmi A | Assay to Screen Ligands that Selectively Activate Opioid Receptor Heterodimers | 17148456 & 17329545 |
| Engelman, Donald M | A High Capacity Screen for Membrane-Active Compounds | |
| Gupta, Vineet | Developing HTS Assays for Discovery of Small Molecule Regulators of Integrins | 17438069 |
| Jarstfer, Michael B | A High Throughput Screen for Telomerase Assembly | 16620757 |
| Khanna, Pyare L | HTS Cell Based EFC Assays for GPCR Drug Discovery | |
| Kampf, J Patrick | A Fluorescent HTS Assay for the Discovery of FABP Binding Inhibitors | |
| Kan, Chen-Chen | Human CD4+ T Cell Based High Throughput Assay for Drug-Resistant HIV-1 Proteases | |
| Katz, Richard A | GFP-Based Assays to Probe Transcriptional and Post-Transcriptional Controls | |
| Lansbury, Peter T | A High-Throughput Assay for SOD1 Aggregation Inhibitors | |
| Marsh-Armstrong, Nicholas R | Photoreceptor Degeneration Assay in Transgenic Xenopus Reporter Line | |
| Mckerrow, James H | High Throughput Assay for Screening Compounds Against T. Brucei | 16784460 |
| Mecsas, Joan C | Inhibitors of Yersinia Yop Type III Secretion and Translocation | |
| Mohan, Royce | Novel High Content Vascular Patterning Assay | |
| Morris, David G | High Throughput Molecular Screening for Compounds that Alter Tgfb1 Signaling Tgfb1 Signaling | |
| Niswender, Colleen M | A Direct Assay for HTS of Gi/Go-linked GPCRs: mGluR7 as the Prototype | 17416742 |
| Pasquale, Elena B | EphA4 Receptor Antagonists for CNS Regeneration | |
| Scharenberg, Andrew M | TRPM2 HTS Screening Assay Development | |
| Schmid, Molly B | Genetic-Based Whole Cell Assays for Discovery of Novel Antibacterials | |
| Schmidt, Walter K | HTS-Based Identification of Novel Rce1p Inhibitors | |
| Siderovski, David P | Real-Time Fluorescence Assays of RGS Domain GAP Activity | 17660054 |
| Sperandio, Vanessa | Screen for Quorum Sensing Molecular Inhibitors | |
| Stivers, James T | High Throughput Assay for Topoisomerase Enzyme Targets | |
| Studer, Lorenz | HTS Screen for Neural Differentiation in Human ES Cells | |
| Swaan, Peter W | High-Throughput Assay for the Intestinal Peptide Transporter | |
| Trubetskoy, Vladimir S | Development of a Robust HTS Assay to Profile Glucuronidation of Small Molecules | 17638534 & 17207411 |
| Waldman, Todd | Isogenic Cell-Based Screens for Cancer - Targeting Oncogenic B-Catenin | |
| Weis, Karsten | Using Chemical Biology to Study the Small GTPase Ran | |
| Xie, Xinmin S | Development of HTS Assay for K(ATP) Channels Using FLIPR | |
| Ye, Qi-Zhuang | A Fluorescence Polarization Assay for Methyltransferases | |
| Zacharias, David A | A Cell-Based HT Imaging Assay for Palmitoylation | |
| Agaisse, Herve F | High-throughput screen for compounds affecting intracellular pathogen infection | |
| Aiken, Christopher R | Discovering Novel Inhibitors of HIV-1 Maturation | |
| Ayad, Nagi G. | Small-molecule Inhibitors of Wee1 Degradation and Mitotic Entry | |
| Balk, Steven P. | HTS for Androgen Receptor Antagonists that Recruit NCoR | |
| Bottini, Nunzio | Fluorogenic PTP Assay for Use in HTS of Novel LYP Inhibitors | |
| Brown, Steven J. | Development of a High Throughput Screening Galanin 3 Receptor Assay | |
| Crawford, Brett E. | Development of cell-based assays for discovery of GIcNAc-TV inhibitors | |
| Cunningham, Kyle W | Assays for compounds that block or stimulate yeast cell death | |
| Day, Billy W | High Throughput/Content Screens for Dynein Inhibitors | |
| Delisa, Matthew P. | A cell-based screen for inhibitors of intracellular Abeta aggregation | |
| Denton, Jerod S. | Identification of novel modulators of ROMK K+ channel activity | |
| Deshmukh, Mohanish P. | Chemical Probes for Uncovering Differential Regulators of Apoptosis in Cells | |
| Djaballah, Hakim | Novel & Selective Small Molecular Inhibitors of Human Peptide Deformylase | |
| Hodgson, Louis | Screening for RhoC Activation and its modulation by GEFs | |
| Hoffmann, F. Michael | An HTS Assay for Inhibitors of Smad-dependent Transcriptional Responses to TGF-beta | |
| Hogenesch, John B. | A Dual Transcriptional and High Content Assay for Cryptochrome | |
| Hughes, Robert E. | A cell-based screen for small molecule binders of mutant huntingtin messenger RNA | |
| Jegla, Timothy J. | Development of HTS Assays for Sub-Threshold Potassium Channels | |
| Johnson, Gary L. | Inhibitor Screens for Five MAPK Kinase Kinases Important in Human Disease | |
| Khanna, Pyare L | HTS Technology for Discovery of Drugs Targeting GPCR Oligomers | |
| Landick, Robert C. | High-Throughput Identification of RNA polymerase inhibitors in vivo | |
| Levine, Fred | High-Throughput Screen for Beta-Cell Replication | |
| Linder, Maurine E. | Assay Development to Identify Palmitoylation Inhibitors of Neuronal Proteins | |
| Luo, Hongbo R | High throughput screening for inhibitors of Akt plasma membrane translocation | |
| Marzluff, William F. | Screen for molecules inhibiting histone pre-mRNA processing | |
| Mcneil, Michael R. | Glucosamine-1-phosphate and serine acetylases: HTS assays and configurations | |
| Nettles, Kendall W. | Assay Development for Identification of ER-NFkB Pathway Selective Agents | |
| Neubig, Richard R. | Multiplexed flow cytometry screens for RGS inhibitors | |
| Nikolovska-Coleska, Zaneta | Discovery and characterization of novel small molecule inhibitors of Mcl-1 | |
| Padgett, Richard A. | Screen for Small Molecule Inhibitors of Mammalian Spliceosomes | |
| Perrimon, Norbert | High-throughput screening assay development for axonopathic neurodegeration | |
| Salavati, Reza | RNA as the catalyst for screening drugs against trypanosomatids | |
| Thacher, Scott M. | Small Molecule Screen for Circadian and Metabolic Transcription Factors | |
| Traynelis, Stephen F. | Identification of protease activated receptor-2 modulators | |
| Wahlestedt, Claes | Assay Development Relating to the HTS of the Neuropeptide Y-Y2 Receptor | |
| Weiss, Eric L. | Development of a robust high throughput assay for the discovery of RAM network inhibitors | |
| Wells, James A. | Activators of Procaspase-7 | |
| Wessling-Resnick, Marianne | Fluorescence-based screen to probe hepcidin-ferroportin interactions | |
| Williamson, James R. | HTS for Discovery of Inhibitors of STAR Protein-RNA complexes | |
| Xie, Xinmin Simon | Development of HTS Platform for Human Fatty Acid Transport Protein 4 Using FLIPR | |
| Zhu, Michael X. | High throughput screening of ligands of TRP channels | |
| Arany, Zoltan P | High throughput screening for modulators of the transcriptional coactivator PGC-1 | |
| Blenis, John | Development of a high content cell based screen for inhibitors of the mTOR signal | |
| Cleary, Michael L | Inhibitors of MLL-Menin Interaction | |
| Fidock, David A | A cell-based HTS for delayed death inhibitors of the malarial parasite plastid | |
| Gerace, Larry R | Screen for Small Molecule Inhibitors of Nuclear Protein Import | |
| Gochin, Miriam | High-Throughput Screening for Human Immunodeficiency Virus Fusion Inhibitors | |
| Harris, Jason B | Development of a small molecule screen for PhoP regulon inhibitors in Salmonella | |
| Hodder, Peter Simmons | HTS assays for discovery of novel beta-lactamase inhibitors via click chemistry | |
| Huang, Qihong | A Cell-based Screen for Small Molecule Modulators of the miRNA Pathway | |
| Jain, Anjali | Functional Genomics Tools for HER2 heterodimers and Androgen Receptor Signaling | |
| Jardetzky, Theodore S | HTS for Small Molecule Modulators of EB Virus Protein-Protein Interactions | |
| Kampf, J Patrick | An HTS Assay for the Discovery of Specific Inhibitors of Adipocyte FABP | |
| Li, Rongbao | HTS Assay Development for Discovery of Specific PYK2 Inhibitors | |
| Peterson, Jeffrey R | Allosteric, Small-Molecule Inhibitors of Actin Nucleation by the Formin mDia1 | |
| Piazza, Gary A | A Novel HTS Cell-Based Assay For Cyclic GMP | |
| Rogers, Jack T | MLSN Screen of the PD Alpha Synuclein 5'UTR | |
| Rogers, Michael S | Assay for Inhibitors of Angiogenesis and Anthrax Toxin Receptor 1 | |
| Sander, Chris | High-throughput identification of compounds that modulate the TGF-beta pathway | |
| Wuttke, Deborah S | Development of a HTS Assay Targeting End Protection of Telomeres |
