Small-molecule chemical probes are widely used as research tools to study biological function and disease mechanisms (Strausberg and Schreiber, 2003). Indeed, a major new initiative of the NIH Roadmap project has been the establishment of Molecular Libraries Screening Center Networks (MLSCN) (http://mli.nih.gov/mlscn/index.php). The goals of these centers are to provide academic researchers access to small molecule compound libraries that can be screened using high throughput robotics. Whole-genome RNAi-based libaries are also being used to identify genes involved in a variety of cellular pathways (Ashrafi et al., 2003;Friedman and Perrimon, 2006). However, a major limitation for most researchers is that their biological assays are not compatible or optimized for HTS. This has restricted access for many investigators as the screening centers accept only those assays that are already miniaturized for a multi-well format and shown to produce a robust and reproducible readout that can be quantified with HTS devices. Some considerations important for the development and validation of HTS assays (http://mli.nih.gov/mlscn/index.php) are that the assays should: 1) Be easy to automate with steps such as centrifugation, filtration and extraction avoided;2) Have demonstrated capability of working reproducibly in a 96-, 384-, or 1536-well plate format;3) Have signal of sufficient intensity with a signal-to-background ratio of at least 5 and a coefficient of variation (CV) below 10%;and 4) Have a Z'-factor value in the range of 0.5-1.0. These statistical values take into account both the assay signal dynamic range and the data variation (Zhang et al., 1999). The purpose of Core 6 is to facilitate the development of such assays for NINDS qualifying investigators such that the assays are validated for HTS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Center Core Grants (P30)
Project #
5P30NS045892-10
Application #
8485514
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
10
Fiscal Year
2013
Total Cost
$82,300
Indirect Cost
$26,691
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Song, Liujiang; Llanga, Telmo; Conatser, Laura M et al. (2018) Serotype survey of AAV gene delivery via subconjunctival injection in mice. Gene Ther 25:402-414
Zhang, Jing; Wu, Tao; Simon, Jeremy et al. (2018) VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma. Science 361:290-295
Boyer, Nicholas P; Monkiewicz, Caroline; Menon, Shalini et al. (2018) Mammalian TRIM67 Functions in Brain Development and Behavior. eNeuro 5:
Sidorov, Michael S; Judson, Matthew C; Kim, Hyojin et al. (2018) Enhanced Operant Extinction and Prefrontal Excitability in a Mouse Model of Angelman Syndrome. J Neurosci 38:2671-2682
Crowther, Andrew J; Lim, Szu-Aun; Asrican, Brent et al. (2018) An Adeno-Associated Virus-Based Toolkit for Preferential Targeting and Manipulating Quiescent Neural Stem Cells in the Adult Hippocampus. Stem Cell Reports 10:1146-1159
Allard, Denise E; Wang, Yan; Li, Jian Joel et al. (2018) Schwann cell-derived periostin promotes autoimmune peripheral polyneuropathy via macrophage recruitment. J Clin Invest 128:4727-4741
Yeh, Chia-Yu; Asrican, Brent; Moss, Jonathan et al. (2018) Mossy Cells Control Adult Neural Stem Cell Quiescence and Maintenance through a Dynamic Balance between Direct and Indirect Pathways. Neuron 99:493-510.e4
Thaxton, Courtney; Kloth, Alexander D; Clark, Ellen P et al. (2018) Common Pathophysiology in Multiple Mouse Models of Pitt-Hopkins Syndrome. J Neurosci 38:918-936
Decot, Heather K; Namboodiri, Vijay M K; Gao, Wei et al. (2017) Coordination of Brain-Wide Activity Dynamics by Dopaminergic Neurons. Neuropsychopharmacology 42:615-627
McCoy, Eric S; Taylor-Blake, Bonnie; Aita, Megumi et al. (2017) Enhanced Nociception in Angelman Syndrome Model Mice. J Neurosci 37:10230-10239

Showing the most recent 10 out of 158 publications