Molecular Screening Shared Resource

The MSSR provides a comprehensive range of high-throughput screening (HTS) services including chemical genomics, functional genomics, and drug discovery.

High-Throughput Screening | Drug Discovery | Functional Genomics

Molecular Screening Shared Resource

The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of high-throughput screening (HTS) services including chemical genomics, functional genomics, and drug discovery. The MSSR is an open environment and welcomes academic investigators from UCLA as well as from all over the globe. Industrial clients are equally welcome as the MSSR is set up as a fee for service entity and does not retain intellectual property. In conjunction with the Center for Environmental Implications of Nanotechnology, the MSSR is currently the only HTS facility in the nation with an ongoing, dedicated effort towards high-throughput toxicity testing of nanomaterials. The MSSR is a shared resource supported in part by the Jonsson Comprehensive Cancer Center (JCCC) and works with JCCC scientists on oncology related projects. The MSSR offers services that go beyond traditional HTS facilities: for example, we are pursuing the construction of genome-wide deletion libraries of relevant organisms for biofuel production and work in collaboration with equipment and reagent manufacturers on technology development and beta-testing of products.

Services:

DRUG DISCOVERY

Our compound libraries consist of over 180,000 molecules. For the purpose of chemical genomics the MSSR provides annotated small-molecule libraries where the targets are known. Other sets contain over 1,000 FDA approved drugs, a comprehensive set of anti-cancer agents provided by the NCI and over 2,000 purified natural products. For drug discovery projects, the MSSR offers small molecule libraries which target high value classes of proteins such as kinases, proteases, ion channels as well as g-protein coupled receptors (GPCRs). The residual 140,000 compounds are contained in libraries sampling the drug-like chemical space and are filtered for any toxicological liabilities. Over 70% of our compounds are in libraries that were custom selected for the MSSR and are not likely to be found in another screening facility.

FUNCTIONAL GENOMICS

In addition to drug discovery and chemical genomics, the MSSR provides functional genomics libraries using inhibitory RNA (RNAi) for gene KO and the complementary cDNA overexpression methodologies. The MSSR offers three commercially available siRNA libraries covering the human and mouse druggable and the entire mouse genome. Kinases and GPCR’s are available as sub-libraries with 4 siRNA constructs per gene. This enables advanced analysis methodologies such as redundant siRNA analysis (RSA) which allows for elimination of outliers and siRNA’s which might be off-target.

Our arrayed shRNA libraries contain over 60,000 clones targeting about 18,000 genes with an emphasis in coverage on desirable target classes, such as kinases, proteases, phosphatases, GPCRs and ion channels. In addition to the traditional target classes, we offer various custom libraries such as a validated cancer-specific shRNA set of about 150 targets from the NCI and a cancer-specific set of over 2,000 clones covering 500 cancer-related genes selected by the Sanger Institute. Other sublibraries cover transcription factors, ubiquitinization and de-ubiquitinization pathways, apoptosis, etc. These libraries are proprietary to the MSSR as they were custom selected and arrayed at the MSSR. The capability of customizing shRNA libraries enables the MSSR to tailor shRNA libraries to the needs of a particular Principal Investigator.

The MSSR offers a mixed mouse and human cDNA genome-wide collection for screening. The library covers about 16,000 full length cDNA clones custom arrayed at the MSSR. Such a cDNA overexpression library is essential for gain-of-function (GOF) screens, which are complementary to loss-of-function RNAi strategies. The MSSR has as well arrayed genome wide Knockout or deletion libraries of the model system E.Coli and S.Cervisiae available. These libraries contain all non-essential genes and are especially useful for nanotoxicology studies as they offer insight into the mechanism of nanotoxicity.

SPECIALIZED EQUIPMENT

Two Beckman CORE systems with a throughput of over 100,000 samples a day are the foundation of our automation equipment employed by the MSSR. These systems consist of high-end multi-mode plate readers addressing all available readouts, liquid handlers, bulk-dispensers, a plate washer, and automated CO2 incubators. The systems are controlled by Beckman-Coulter SAMI scheduling software, which allows for 24/7 walk-away automation. The systems are configured for maximal flexibility and allow for all assay workflows conceivable and automated hitpicking is incorporated. An Acumen Explorer high-content screening system and an Image Xpressmicro highcontent screening system allow for image-based screening. This is especially important in functional genomics where frequently only a cellular phenotype is known. The Acumen is currently integrated with a Twister robot allowing for 80 plate capacity. Another liquid-handling integrated system consisting of a Velocity 11 Benchcell plate handling robot with Vprep liquid handler, PlateLoc plate sealer and Vcode barcoder are housed in a custom HEPA-filtered Biosafety cabinet and are used for aliquoting our shRNA libraries into plates once the libraries are in lentiviral form. Other liquid handlers such as the Precision 2000, two Qbot colony pickers and a Hydra 96 with XY platform are available for use as well.
Center Highlights
  • High-Throughput-Screening
  • Drug Discovery
  • Functional Genomics & Novel Applications
  • User base includes: Small BioTech, Big Pharma, Academics, NIH
  • Chemical Libraries: 180,000 compounds of drug-like molecules with emphasis on desirable target classes such as kinases, proteases, phosphatases, GPCRs and ion channel
  • cDNA overexpression library of 16,000 clones accessible as "expression-ready" sets
  • Plater reader based readouts and high content screening
Work performed at the MSSR has supported numerous publications in top notch journals such as Nature Biotechnology, Science, PNAS, amongst others


High-Throughput Screening | Drug Discovery | Functional Genomics

The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of high-throughput screening (HTS) services including chemical genomics, functional genomics, and drug discovery. The MSSR is an open environment and welcomes academic investigators from UCLA as well as from all over the globe. Industrial clients are equally welcome as the MSSR is set up as a fee for service entity and does not retain intellectual property. In conjunction with the Center for Environmental Implications of Nanotechnology, the MSSR is currently the only HTS facility in the nation with an ongoing, dedicated effort towards high-throughput toxicity testing of nanomaterials. The MSSR is a shared resource supported in part by the Jonsson Comprehensive Cancer Center (JCCC) and works with JCCC scientists on oncology related projects. The MSSR offers services that go beyond traditional HTS facilities: for example, we are pursuing the construction of genome-wide deletion libraries of relevant organisms for biofuel production and work in collaboration with equipment and reagent manufacturers on technology development and beta-testing of products.

Center Highlights
  • High-Throughput-Screening
  • Drug Discovery
  • Functional Genomics & Novel Applications
  • User base includes: Small BioTech, Big Pharma, Academics, NIH
  • Chemical Libraries: 180,000 compounds of drug-like molecules with emphasis on desirable target classes such as kinases, proteases, phosphatases, GPCRs and ion channel
  • cDNA overexpression library of 16,000 clones accessible as "expression-ready" sets
  • Plater reader based readouts and high content screening

Services:

DRUG DISCOVERY

Our compound libraries consist of over 180,000 molecules. For the purpose of chemical genomics the MSSR provides annotated small-molecule libraries where the targets are known. Other sets contain over 1,000 FDA approved drugs, a comprehensive set of anti-cancer agents provided by the NCI and over 2,000 purified natural products. For drug discovery projects, the MSSR offers small molecule libraries which target high value classes of proteins such as kinases, proteases, ion channels as well as g-protein coupled receptors (GPCRs). The residual 140,000 compounds are contained in libraries sampling the drug-like chemical space and are filtered for any toxicological liabilities. Over 70% of our compounds are in libraries that were custom selected for the MSSR and are not likely to be found in another screening facility.

FUNCTIONAL GENOMICS

In addition to drug discovery and chemical genomics, the MSSR provides functional genomics libraries using inhibitory RNA (RNAi) for gene KO and the complementary cDNA overexpression methodologies. The MSSR offers three commercially available siRNA libraries covering the human and mouse druggable and the entire mouse genome. Kinases and GPCR’s are available as sub-libraries with 4 siRNA constructs per gene. This enables advanced analysis methodologies such as redundant siRNA analysis (RSA) which allows for elimination of outliers and siRNA’s which might be off-target.

Our arrayed shRNA libraries contain over 60,000 clones targeting about 18,000 genes with an emphasis in coverage on desirable target classes, such as kinases, proteases, phosphatases, GPCRs and ion channels. In addition to the traditional target classes, we offer various custom libraries such as a validated cancer-specific shRNA set of about 150 targets from the NCI and a cancer-specific set of over 2,000 clones covering 500 cancer-related genes selected by the Sanger Institute. Other sublibraries cover transcription factors, ubiquitinization and de-ubiquitinization pathways, apoptosis, etc. These libraries are proprietary to the MSSR as they were custom selected and arrayed at the MSSR. The capability of customizing shRNA libraries enables the MSSR to tailor shRNA libraries to the needs of a particular Principal Investigator.

The MSSR offers a mixed mouse and human cDNA genome-wide collection for screening. The library covers about 16,000 full length cDNA clones custom arrayed at the MSSR. Such a cDNA overexpression library is essential for gain-of-function (GOF) screens, which are complementary to loss-of-function RNAi strategies. The MSSR has as well arrayed genome wide Knockout or deletion libraries of the model system E.Coli and S.Cervisiae available. These libraries contain all non-essential genes and are especially useful for nanotoxicology studies as they offer insight into the mechanism of nanotoxicity.

SPECIALIZED EQUIPMENT

Two Beckman CORE systems with a throughput of over 100,000 samples a day are the foundation of our automation equipment employed by the MSSR. These systems consist of high-end multi-mode plate readers addressing all available readouts, liquid handlers, bulk-dispensers, a plate washer, and automated CO2 incubators. The systems are controlled by Beckman-Coulter SAMI scheduling software, which allows for 24/7 walk-away automation. The systems are configured for maximal flexibility and allow for all assay workflows conceivable and automated hitpicking is incorporated. An Acumen Explorer high-content screening system and an Image Xpressmicro highcontent screening system allow for image-based screening. This is especially important in functional genomics where frequently only a cellular phenotype is known. The Acumen is currently integrated with a Twister robot allowing for 80 plate capacity. Another liquid-handling integrated system consisting of a Velocity 11 Benchcell plate handling robot with Vprep liquid handler, PlateLoc plate sealer and Vcode barcoder are housed in a custom HEPA-filtered Biosafety cabinet and are used for aliquoting our shRNA libraries into plates once the libraries are in lentiviral form. Other liquid handlers such as the Precision 2000, two Qbot colony pickers and a Hydra 96 with XY platform are available for use as well.