Director: Robert Damoiseaux, Ph.D.

Mailing Address
California NanoSystems Institute
570 Westwood Plaza
Bldg 114 Room 6310

Telephone: (310) 794-1974 
Email: rdamoiseaux@mednet.ucla.edu

Hours of Operation
9:00 a.m. to 5:00 p.m. PST, Mon to Fri

Major Services

The Molecular Screening Shared Resource (MSSR) delivers high throughput screening to the UCLA research community. Features of the MSSR include:

High Throughput Screening (HTS) Technology

The services provided include the use of high throughput screening (HTS) technology, a total of over 200,000 compounds in various libraries, arrayed genome wide sets for CRISPR, cDNA, shRNA and siRNA for mouse and/or human. We also perform data analysis and cheminformatics taking advantage of deep learning approaches using AI and neuronal networks. Please use the links above to find out more about the MSSR.

Chemical Libraries

The libraries available at the MSSR cover FDA approved drugs for re-purposing, chemical genomics libraries for dissecting biological pathways, and various larger libraries for drug discovery. We also offer libraries of drugs in clinical trials such as kinase inhibitors.

Databases

The MSSR maintains databases of all assays run and their results. By cross referencing and collaborating with researchers who employed related assays, additional information may be gained providing deeper insight into processes fundamental to health and disease.

Funded by numerous departments

The MSSR is currently funded by the JCCC, the Department of Molecular and Medical Pharmacology, the Department of Microbiology, Immunology and Molecular Genetics, and the Dean’s office, David Geffen School of Medicine and the California NanoSystems Institute.

OPERATING POLICIES

Consultations

Consultations are free, and we strongly suggest that you take advantage of the service. During this initial appointment, we’ll discuss your target of interest, libraries, general screening procedures, assay adaptation (if needed) and controls (if needed).

Scheduling

Instrument time and library screens must be scheduled at least a week in advance. This allows time to consult, adapt the assay to high throughput mode and run controls, if necessary. Scheduling a consultation appointment well in advance (2 weeks or more) of the projected screen date is advised.

Cancellations

Cancellations should be made at least 24 hours in advance. Chemical libraries must be thawed in order to perform a screen. Each freeze-thaw cycle has the potential to damage chemical entities in the libraries. By canceling before the libraries are thawed, we avoid unnecessary risk to the libraries. In addition, by canceling in advance, other users can schedule to use instruments and to perform screens. So, please be considerate.

Access Prioritization

The MSSR has so far been able to accommodate all requests. Should the need arise, the MSSR advisory board will resolve prioritization conflicts.

Please note that library handling and instrument operation are by MSSR personnel and trained users only.

Acknowledgements/Grants

If you plan to write a grant or write a paper including the screening you plan to perform at the MSSR, please let us know. We need to keep records of these. Such records are needed when we apply for money to support the MSSR. Recharge does not cover the entire cost of running a screen. Please help us to keep the costs to users as low as possible.

EXPERTISE

The Director of the MSSR, Robert Damoiseaux, is an HTS expert with an extensive background in the industry. His research interests are focused on the development of novel HTS technologies, and he is committed to supporting the HTS needs of JCCC and UCLA investigators by implementing these technologies and providing guidance and oversight to all projects. Damoiseaux received his Ph.D. at the University of Lausanne under Dr. Kai Johnsson (now Director of the Max Planck Institute for Medical Research, Munich) and then joined the Institute for Functional Genomics where he was in charge of the development of the next generation assay platform for proteases. He authored >100 manuscripts and patents on HTS and synthesis, and was recognized as an expert author in Wiley’s Development of Therapeutic Agents Handbook. Damoiseaux is a member of the cancer center, the California NanoSystems Institute (CNSI) and the Crump Institute for Molecular Imaging, and was also a member of the NIH study section and special emphasis panel reviewing HTS grants. He is a frequent co-investigator and co-PI on grants with JCCC members, and these grants provide additional stability to the MSSR as they provide funding for projects and associates.

Currently, the MSSR staff includes Connie Yuen, a Berkeley trained Masters Research Associate, provides hands-on expertise in assay development, screening execution, and library management, and David Austin, Ph.D. (formerly of Vanderbilt), who has significant experience in prostate cancer and provides support for assay development. David is also tasked with developing high throughput cell line generation capabilities and CRISPR-based screening approaches.

EQUIPMENT

Thermo Spinnaker System 1

• Flex Station II: 96 and 384 well plate reader (Molecular Devices): GPCR and ion channel assays and general fluorescence applications.
• Victor 3V: 96 or 384 and 1536 well : UV-VIS absorbance, luminescence, fluorescence polarization, fluorescence, time resolved fluorescence assay.
• Biomek FX: Liquid handler for compound transfer and cherry picking. It is equipped with a custom built pin tool and transfers 384 compounds in 85 seconds.
• Thermo Spinnaker robotic arm on a rail: delivers and transfers plates from plate hotels or incubators onto the liquid handlers, plate readers, etc.
• Liconic STX 220: CO2 plate incubator with a capacity of 220 plates. Multidrop 384: (Thermo LabSystems): manifold liquid dispensing. This instrument is useful for accurately delivering a fixed amount of liquid rapidly (about 25 seconds) into either 96 or 384 well plates and plating of cells.
• ELx 405 plate washer, Bio-Tek Instruments: well washing, aspiration, dispensing. This instrument would be useful in performing assays which require multi-step aspiration from and dispensing into wells.
• Lidding station: Automated storage of lids.

Thermo Spinnaker System 2

An linear rail based system which is dedicated to high-content screening.

• ImageXpress Confocal (Molecular Devices): A high throughput spinning disk microscope that also doubles as wide field microscope and can be used for phenotypic screens requiring optical sectioning, subcellular localization, mitochondrial morphology evaluation and other demanding applications. We have over 200TB storage capacity integrated and high speed data analysis capabilities as well as custom module editor software to simplify complex analysis workflows.
• Envision: High speed plate reader for 96 or 384 and 1536 well plates in the following modes: UV-VIS absorbance, luminescence, fluorescence polarization, fluorescence, time resolved fluorescence assay as well as alpha screening.
• Thermo Spinnaker robotic arm on a rail: delivers and transfers plates from plate hotels or incubators onto the liquid handlers, plate readers, etc.
• Cytomat 6001: CO2 plate incubator with a capacity of over 180 plates.
• ELx 406 plate washer, Bio-Tek Instruments: well washing, aspiration, dispensing. This instrument would be useful in performing assays which require multi-step aspiration from and dispensing into wells. It is also equipped with dual syringe dispensers as well as a peristaltic pump for reagent addition.

Other instrumentation available:

• Qbot: Colony picker and arrayer (Genetix). This instrument has a 72 plate capacity and is used in high-throughput sequencing projects as well as for library construction and maintenance. It uses 96 and 384 well plates, omni-trays and is equipped with a video camera for automated colony recognition and blue-white screening.
• Precision 2000: A 12 channel liquid handler (Bio-Tek) which can be used in a steril bench and adresses 96 and 384 well plates.
• Various Multidrop 384's: (Thermo LabSystems) This instrument is useful for accurately delivering a fixed amount of liquid rapidly into either 96 or 384 well plates and plating of cells.
• Acumen Explorer (TTP Labtech): This laser scanning cytometer is currently the fastest high content screening system available. It enables cell-by-cell readouts resulting in a flow-cytometer like data structure useful for phenotypic screening. Examples are screens based on translocation events from the nucleus to the cytosol, cytotoxicity screens and even cell cycle based screening is possible.
• ImageXpress (Molecular Devices): A high throughput epifluorescence microscope which can be used for phenotypic screens requiring the highest quality images such as neurite outgrowth, translocation and certain cell toxicity screens. We have a phase contrast option enabling label free phenotypic screening of zebrafish. Using special objectives and analysis modules, even difficult phenotypes such as the of uptake of bacteria by mammalian cells can be quantified. This systen is integrated with an incubator using a custom Denso robotic arm.
• Biosorter (Union Biometrica): The BioSorter® is a continuous flow system capable of analyzing, sorting and dispensing objects ranging in size from 10 to 1,500 µm. It is useful for sorting zebrafish, C.Elegans, organoids, spheroids and other large objects based on either fluorescence or backscatter/size. Moreover, the MSSR has fitted this biosorter with an in house built aerosol management system that enables us to sort live particles into 96 or even 384 well plates and we can define the number of objects and characteristics of the objects on a per well level enabling screening of large biological objects with defined parameters.
• More fully integrated online systems tailored to RASLSeq and Antibody screening are currently being implemented—check back often!

Our compounds libraries are split into four segments: Pharmacological validation and repurposing libraries (LOPAC, Prestwick and Microsource spectrum, 430 clinical kinase inhibitors annotated with targets), targeted libraries for high value protein classes,  lead-like libraries, and diverse libraries and diverse/smart libraries. All of our compounds are at least 90 percent pure. On average, we can resupply 90 to 95 percent of the hit compounds as powder for follow up. With the exception of the diverse library (UCLA set) which is a pre-plated set, all of our sets are custom sets and are not likely to be found in another screening facility. We have applied extensive filtering against liabilities such as reactive groups, aggregators etc. The drug-likeness and usefulness of our pharmacological validation and re-purposing libraries as well as our custom libraries is well established. We found a historic sucess rate of about 90 to 95 percent in delivering tractable hits from our libraries across all targets.

Just in—Human Genome wide arrayed CRISPER library!

We are pleased to offer access to a full genome wide arrayed CRISPR library with a unique two guide per construct design! We will be updating this section as we build out the sub-libraries. Individual clones for your targets and subsets are also available for screening!

There is a tiered fee structure. Costs for JCCC members are listed below; for non-members, please refer to our [website link TBD] for details.