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
Burette, Alain C; Park, Haram; Weinberg, Richard J (2014) Postsynaptic distribution of IRSp53 in spiny excitatory and inhibitory neurons. J Comp Neurol 522:2164-78
Wright, Brittany D; Loo, Lipin; Street, Sarah E et al. (2014) The lipid kinase PIP5K1C regulates pain signaling and sensitization. Neuron 82:836-47
Huang, Hsien-Sung; Yoon, Bong-June; Brooks, Sherian et al. (2014) Snx14 regulates neuronal excitability, promotes synaptic transmission, and is imprinted in the brain of mice. PLoS One 9:e98383
Mabb, Angela M; Kullmann, Paul H M; Twomey, Margaret A et al. (2014) Topoisomerase 1 inhibition reversibly impairs synaptic function. Proc Natl Acad Sci U S A 111:17290-5
Zhu, Hu; Pleil, Kristen E; Urban, Daniel J et al. (2014) Chemogenetic inactivation of ventral hippocampal glutamatergic neurons disrupts consolidation of contextual fear memory. Neuropsychopharmacology 39:1880-92
Demyanenko, Galina P; Mohan, Vishwa; Zhang, Xuying et al. (2014) Neural cell adhesion molecule NrCAM regulates Semaphorin 3F-induced dendritic spine remodeling. J Neurosci 34:11274-87
Larsen, Rylan S; Smith, Ikuko T; Miriyala, Jayalakshmi et al. (2014) Synapse-specific control of experience-dependent plasticity by presynaptic NMDA receptors. Neuron 83:879-93
McNeill, Robert S; Schmid, Ralf S; Bash, Ryan E et al. (2014) Modeling astrocytoma pathogenesis in vitro and in vivo using cortical astrocytes or neural stem cells from conditional, genetically engineered mice. J Vis Exp :
Gama, Vivian; Swahari, Vijay; Schafer, Johanna et al. (2014) The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. Sci Signal 7:ra67
Morgan-Smith, Meghan; Wu, Yaohong; Zhu, Xiaoqin et al. (2014) GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation. Elife 3:e02663

Showing the most recent 10 out of 54 publications