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High-throughput screening
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==Increasing use of HTS in academia for biomedical research== HTS is a relatively recent innovation, made feasible largely through modern advances in robotics and high-speed computer technology. It still takes a highly specialized and expensive screening lab to run an HTS operation, so in many cases a small- to moderate-size research institution will use the services of an existing HTS facility rather than set up one for itself. There is a trend in academia for universities to be their own drug discovery enterprise.<ref name="Dove2007">{{cite journal|last1=Dove|first1=Alan|title=High-throughput screening goes to school|journal=Nature Methods|volume=4|issue=6|year=2007|pages=523β532|issn=1548-7091|doi=10.1038/nmeth0607-523|s2cid=28059031|doi-access=free}}</ref> These facilities, which normally are found only in industry, are now increasingly found at universities as well. [[UCLA]], for example, features an open access HTS laboratory Molecular Screening Shared Resources (MSSR, UCLA), which can screen more than 100,000 compounds a day on a routine basis. The open access policy ensures that researchers from all over the world can take advantage of this facility without lengthy intellectual property negotiations. With a compound library of over 200,000 small molecules, the MSSR has one of the largest compound deck of all universities on the west coast. Also, the MSSR features full functional [[genomics]] capabilities (genome wide siRNA, shRNA, cDNA and CRISPR) which are complementary to small molecule efforts: Functional genomics leverages HTS capabilities to execute genome wide screens which examine the function of each gene in the context of interest by either knocking each gene out or overexpressing it. Parallel access to high-throughput small molecule screen and a genome wide screen enables researchers to perform target identification and validation for given disease or the mode of action determination on a small molecule. The most accurate results can be obtained by use of "arrayed" functional genomics libraries, i.e. each library contains a single construct such as a single siRNA or cDNA. Functional genomics is typically paired with high content screening using e.g. [[fluorescence microscope|epifluorescent microscopy]] or laser scanning cytometry. The University of Illinois also has a facility for HTS, as does the University of Minnesota. The Life Sciences Institute at the University of Michigan houses the HTS facility in the Center for Chemical Genomics. Columbia University has an HTS shared resource facility with ~300,000 diverse small molecules and ~10,000 known bioactive compounds available for biochemical, cell-based and NGS-based screening. [[The Rockefeller University]] has an [[open access (infrastructure)|open-access]] HTS Resource Center HTSRC (The Rockefeller University, [[HTSRC]]), which offers a library of over 380,000 compounds. Northwestern University's High Throughput Analysis Laboratory supports target identification, validation, assay development, and compound screening. The non-profit Sanford Burnham Prebys Medical Discovery Institute also has a long-standing HTS facility in the [[Conrad Prebys Center for Chemical Genomics]] which was part of the MLPCN. The non-profit [[Scripps Research]] Molecular Screening Center (SRMSC)<ref name="pmid30682260">{{cite journal|vauthors=Baillargeon P, Fernandez-Vega V, Sridharan BP, Brown S, Griffin PR, Rosen H | display-authors=etal| title=The Scripps Molecular Screening Center and Translational Research Institute. | journal=SLAS Discov | year= 2019 | volume= 24 | issue= 3 | pages= 386β397 | pmid=30682260 | doi=10.1177/2472555218820809 | pmc=7724958| s2cid=59274228| doi-access=free }}</ref> continues to serve academia across institutes post-MLPCN era. The SRMSC uHTS facility maintains one of the largest library collections in academia, presently at well-over 665,000 small molecule entities, and routinely screens the full collection or sub-libraries in support of multi-PI grant initiatives. In the United States, the [[National Institutes of Health]] or NIH has created a nationwide consortium of small-molecule screening centers to produce innovative chemical tools for use in biological research. The Molecular Libraries Probe Production Centers Network, or MLPCN, performs HTS on assays provided by the research community, against a large library of small molecules maintained in a central molecule repository. In addition, the NIH created the [[National Center for Advancing Translational Sciences]] or NCATS, housed in Shady Grove Maryland, that carries out small molecule and [[RNAi]] screens in collaboration with academic laboratories. Of note, the small molecule screening uses 1536 well plates, a capability rarely seen in academic screening laboratories that allows one to carry out quantitative HTS in which each compound is tested across four- to five-orders of magnitude of concentrations.<ref name="ReferenceA" />
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