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Laboratory

UCSC Chemical Screening Center: The CSC is a core facility (RRID SCR_021114) serving the research community at UCSC and beyond, supported by the California Institute for Quantitative Biosciences and the UCSC Physiological and Biological Sciences Division.

The CSC has a total of ___sq. ft. of laboratory space on the fourth floor of the recently constructed (2006) Physical Sciences Building (PSB). The lab space includes 2 6-ft fume hoods, house utilities (deionized water, air, vacuum), ___ linear ft. of open bench space plus ___ linear ft. of bench space with table-t0p instrumentation, shelving, and an adjacent space for supplies storage (___sq. ft.). Other labs on the same floor provide us with a tissue culture room, ice machine, and autoclave, and within our building we have flammable storage cabinets (in a room specifically designed for flammables storage), liquid nitrogen, dry ice, access to a balance and pH station, and a cold room. Our building also houses the mass spectrometry facility, NMR facility, X-ray crystallography facility, and macromolecular structure and function facility, and adjacent buildings house the microscopy facility and flow cytometry facility.

The center is supervised by Scott Lokey, Professor of Chemistry, and managed by Beverley Rabbitts, a PhD-level scientist who assists with project design, protocol development, sample preparation, instrument training, and data interpretation. Shared instruments are available to trained users 24/7 on a recharge fee per hour of use basis. 

The facility houses a compound collection that includes 8,000 known bioactives from TargetMol; 2,000 known bioactives from SelleckChem; 87,000 drug-like diversity compounds from ChemDiv; 1,262 low molecular weight fragment compounds from Kevin Gardner and Life Chemicals, 400 cyclic peptides from the lab of Scott Lokey, and a growing collection of marine and terrestrial natural products from the labs of Phil Crews, John MacMillan, Roger Linington (now at Simon Fraser University), and others. Compounds are typically provided as 10mM or 10mg/ml stocks in DMSO in 384-well daughter microplates with minimal number of freeze-thaw cycles.

High throughput screening (HTS) robotics are used to test up to 50,000 compounds per day to identify biologically active compounds targeted towards a variety of biological systems, with legacy data available for comparison. The CSC houses an Echo 650 acoustic dispenser at a robotic sample-preparation workstation, two high throughput imagers including a robot-automated Opera Phenix Plus confocal, two EnVision plate readers, three pipetting robots, 6 bulk liquid handling instruments, image analysis and bioinformatics tools and software, and more (see equipment list for details).

Office

The Chemical Screening Center has ___ sq. ft. office (PSB456) on the same floor near the CSC wetlab (PSB465). This office has desk space for 3 researchers, including one shared user workstation, a desk for the CSC manager, and a desk for research staff working in the CSC. In addition to lab benches, the CSC wetlab has two desks for data analysis work. Administrative support is available through the Department of Chemistry and Biochemistry.

Computer

The Chemical Screening Center has … (in progress!)

• For viewing images/compounds/etc. of CP data: CP-ImageView App
• For looking at a list of immunoCP run contents: immuno-CP contents
• For viewing heatmaps of plate reader scans, with associated chemical structures, we previously developed Halo384 Compare. This is no longer publicly available at the old link – please contact us for access.

Go here for UCSF Pharmacy microsites, which includes:

• QB3 HiTS
• HiTS Natural Product Search Engine
• SMDC HiTS

Looking for the Pipeline Pilot WebPort? Please email us for more information.

COMING SOON: Signals software for quantitation and statistical analysis of high throughput screen image data. Includes deep learning algorithms to identify cell phenotypes.

Users can access several PC options for data analysis, such as with MetaXpress image analysis software packages, FileZilla for server uploads, and TeamViewer  remote control (please enquire to get the ID and password of the one(s) you need). The image data server is housed by a PC located in the lab, next to the imaging computer. Three analysis computers located in the CSC office space are networked and able to process batch jobs together for faster computing.

We have two dongles for MetaXpress image analysis software, with five seats. The package purchased including image segmentation, multiwavelength scoring of cell objects, and automated batch processing. We have curated custom modules, or journals, designed for high throughput, high content phenotype fingerprinting in cytological profiling experiments.

Furthermore, we have developed several in-house tools that can be accessed on our "links" page (also on the menu bar above).

Owned by the MacMillan lab and assisted by the Chemical Screening Center, this facility has a biosafety cabinet, humidified CO2 incubators, brightfield microscope, water bath, and Thermo Locator liquid nitrogen cryo-storage for mammalian cell lines. It is conveniently located on the same floor as the CSC, just two doors down the hallway. Small instruments, such as the MultiDrop, can be carried from the CSC and placed in the hood, as desired.

A variety of 6, 12, 24, 48, 96, 384. and 1536 format multiwell microplate types are available approximately at cost.

Select what is most appropriate for your particular assay…

• plastic colors:
  • white plates for luminescence on the plate reader with top read
  • black plates for fluorescence on the plate reader with top read
  • clear bottom, black plates for inverted fluorescence microscopy
  • clear plates for absorbance
  • clear UV-compatible plates for absorbance at short wavelengths
  • whitish plastic is the most economical and is free of chemical residues left by plastic clearing treatments (e.g. use for compound storage)
• untreated plastic or tissue culture-treated, with or without poly amino acid (e.g. poly-lysine), collagen, or other coatings
• sterile (e.g. for if growing cells in the plate) or not (for short timecourse endpoint assays and toxic reagent storage)
• vented or low-evaporation lids – or without lids (leaving lids out is faster! Plate #1 in the stack serves as the lid for plate #2, and so on)
• well shapes:
  • flat bottom (optimal for endpoint measurements and adherent cells)
  • V bottom (optimal for compound stock plates of small volume)
  • U bottom (optimal for even mixing)
• skirt heights
  • non-skirted for fitting inside PCR machines and other temperature-controlled blocks
  • full-skirted are the most durable
  • half-skirted are better for high magnification imaging (reduce the working distance needed by the objective at the edge wells)
• regular depth, small volume reduced depth, or deep well
• several brands available for each, with slightly different specifications

We also have various types of universal lids and reservoirs for multichannel pipettes.

Please enquire about the plate type you desire, so we can check our inventory and set aside plates for you.

Please be aware of the exact plate product number used, so that appropriate settings can be entered into instruments handling those plates.

We employ full-time expert staff to train and assist you.

• The CSC personnel keep up to date in the fields of high throughput biology, drug discovery, and laboratory automation, and use this knowledge to make strategic choices in acquisitions and upgrades, as well as to make application-specific recommendations to improve your workflows. This partners very nicely with laboratories focused on research questions, rather than technology.
• We painstakingly maintain the fleet of equipment to ensure continuing, reliable resources as much as possible. This includes calibrating and quality control, preventative maintenance, and coordinating repairs. We are intimately knowledgeable on the specific devices housed here, and thus we can help problem solve if issues arise during experiments. In these ways, we are able to provide technologies that would be prohibitively complex to be housed in a lab without staff dedicated to instrument management.
• The resources are made possible by a combination of fees we collect from users, funds from the UCSC Office of Research, NIH and other instrumentation grants, and from philanthropic donors – we are therefore able to provide technology that would be prohibitively expensive to obtain and maintain by an individual lab – technology that is essential to drive modern research forward effectively and competitively.

Compare your dataset from unidentified or novel compounds with data collected by the CSC using known bioactives for guilt-by-association mechanistic insights. We have data collected from a variety of common assays, including cytological profiling and cytotoxicity experiments.

(image from r-bloggers.com)

For high throughput applications, barcodes help reduce human error in sample management. We have a barcode printer, and the printed sticker labels can be manually affixed to your plates, and read by several of our instruments that have onboard barcode reading capability. Alternately, pre-barcoded plates can be purchased, for use on those instruments without the need for printing and sticking labels.

We have established collaborations with numerous esteemed researchers on our campus and beyond.

In 2021, we helped form a cooperative network between core facilities at UCSC. We are proud to be part of the team of core facilities bringing you a range of key resources such as: NMR, cryoEM, crystallography, flow cytometry, light microscopy, scanning electron microscopy, genomics, transgenics, vivarium, optofluidics, isotopes, cell browser, paleogenomics, marine analytics, plasma analytics, COVID testing, a clean room, etc.