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The Center for Integrative Chemical Biology and Drug Discovery (CICBDD)

The Center for Integrative Chemical Biology and Drug Discovery (CICBDD) was created with the mission of bringing dedicated high throughput screening and medicinal chemistry expertise to bear on biological targets of therapeutic relevance under investigation by UNC faculty. Synthetic and computational chemists, and assay development/compound profiling scientists work in the Center and create dedicated, interdisciplinary project teams to progress targets through the probe and drug discovery process. The CICBDD therefore has the staff, equipment and expertise to progress biological targets through the assay development, hit generation and hit-to-lead/probe/lead optimization phases.

 

Lead Discovery and Characterization

LABORATORY

The home of the CICBDD is Marsico Hall, constructed in 2014 and located in the heart of UNC’s biomedical research campus and physically connected to the Lineberger Comprehensive Cancer Center (LCCC). Laboratory accommodations for the Center consist of ~10,000 sq.ft. on the third and fourth floors of Marsico Hall. There are 25 X 6 ft fume hoods and 10 x 8 ft fume hoods, as well as 5 labs for cell culture and a dedicated lab for fluorescence microscopy in this space. The Center also has a dedicated fine chemical storeroom with a bar-coded inventory system and a walk-in -20°C freezer for storage of compound plates. The CICBDD is well equipped for state-of-the-art organic and medicinal chemistry, along with protein expression, biochemical assay development and focused or diversity-based screening.

CBMD
Computational Biophysics and Molecular Design

COMPUTERS

Faculty, Research Staff, Students and Postdoctoral Fellows

All faculty, research staff, students and postdoctoral fellows in the CICBDD have either personal laptops or access to a desk- based computer with network access to all UNC IT resources (e-library, etc.). The CICBDD relies on the vast resources for computational modeling available at UNC. Academic Technology & Networks (ATN), a division of the Office for Information Technology Services, currently offers a number of software packages to support research computing including EMBOSS, DOCK, Clustal, CNSsolve, GCG, Sybyl, InsightII, Genomax, Cerius2 and most InsightII modules for homology-related docking for structural searches and molecular visualization packages such as Spock and Denzo at an annual cost of over $100,000.  Recent ATN hardware commitments in support of computational biology and genomic computing include over $600,000 of the $1.3 million spent upgrading our SGI system to an Origin 3800 with 64 processors and 64 GB of memory, and $60,000 toward the installation of a 184-processor Beowulf Cluster with 184 GB of memory and a Myrinet interconnect, and the acquisition of a 44 processor SUN ES-15000 worth $2.4 million.

 

EQUIPMENT

Lead Discovery & Characterization, Ken Pearce, Director
Medicinal Chemistry, Xiaodong Wang, Director

The Lead Discovery and Characterization Group handles all compound management and is equipped to develop screening assays using industry standard best practices and technologies. The equipment within LD&C is organized around an “islands of automation” concept where each device is capable of walk away operation sufficient to process 30-50 plates. This strategy has been proven to be maximally effective in environments where flexibility is required, and assay formats may vary significantly over time. All equipment is maintained at or above the manufacturers recommended maintenance intervals for testing and calibration.

 

Liquid Handling Instruments

Device Manufacturer Capabilities
 Biomek FX Beckman Coulter 384 well liquid handler for plate replication and reagent dispense
 Freedom EVO Tecan Liquid handler with 2 arms and integrated 96/384 well dispense and transfer head and 8 tip X-Y-Z arm
 Mosquito HTS TTPLabtech Liquid handler capable of nanoliter dispensing and serial dilution in 96, 384, and 1536 well format, including preparation of assay ready plates
 Multimek Nanoscreen 384 well liquid handler for plate replication and reagent dispense
 Multidrop (5) ThermoFisher Automated reagent dispensing with large and small tube dispense heads
 Preddator Redd and Whyte Non-contact nanodispense for reagents
Liquid Handling Equipment
The Mosquito

Plate Reading Instruments/Spectrophotometers

Device Manufacturer Capabilities
 EnVision (2) Perkin Elmer Multilabel reader for AlphaScreen®, fluorescence intensity, fluorescence polarization, time-resolved fluorescence, luminescence (glow, flash and dual luminescence), absorbance; sample dispenser
 Enspire Perkin Elmer Multilabel reader for absorbance, fluorescence, and luminescence
 EZReader Caliper Life Sciences Microfluidic LabChip system utilizing mobility shift assays for enzymatic targets, real-time kinetic data, mechanism of action, kinase profiling
 FLIPR (Roth lab) Molecular Devices Cell based assays including calcium flux, membrane potential and aqueorin
 Azure 600 Azure Bio Systems Fluorescence and chemiluminescence imager for analysis of Western blots, plates, gels
 Patch Express (Roth lab) Molecular Devices High throughput patch clamp for voltage or ligand gated ion channels
 IN CELL Analyzer 2200 GE Lifesciences High content cell imaging system with 3D deconvolution, live cell imaging, and automated sample delivery
 Paradigm Molecular Devices Multilabel reader with absorbance cassette; upgradable for fluorescence, luminescence, western blot capabilities
 ViiA7 Life Technologies Real-Time PCR System for 384 well format qPCR or thermal melt assays
 qTower Analytik Jena Six-fold multiplexing Real-Time PCR System for 96 well format qPCR or thermal melt assays
 QuickDrop Molecular Devices Micro-volume spectrophotometer for quantification of DNA, RNA, oligos, and proteins
 iQue Screener Intellicyte Flow cytometry system capable of multiplexed, high-throughput analysis of cells and beads
Qubit-Flex Thermo Fisher
Benchtop fluorometer can quantify DNA, RNA or protein in 1 to 8 samples simultaneously
 NanoDrop

Thermo Fisher

Micro-volume spectrophotometer for quatification of DNA, RNA, oligos, and proteins
 Ultrasonicator LE220 Covaris Ultrasonicator for compound solutions and DNA shearing
 Analyst GT

Molecular Devices

Multi-mode plate reader; absorbance and fluorescence

Protein Purification

 Akta FPLC/HPLC (3) GE Lifesciences Protein purification using high pressure column chromatography

Compound Storage; Other

 comPOUND TTPLabtech Small tube compound storage unit with random access storage for 200,000+ compounds
 RS Microplate Orbitor Thermo Scientific Automated plate stacker and transporter
 Twister II Perkin Elmer Automated plate mover suitable for integration with numerous instruments
 Plate sealers (2) Thermo Scientific Microplate heat sealer
 Ultrasonicator E-110 Covaris Ultrasonicator for compound solutions and DNA shearing

Chemistry

Device Manufacturer Capabilities
 1260 Series Infinity II LC/MS Agilent Technologies Separate and detect an individual compound rapidly from a mixture; ideal for high-throughput and fast applications
 1260 Infinity II (2) HPLC; Agilent Technologies Compound isolation and purification
 EZ2 Evaporator (2) Genevac Remove solvents to concentrate or dry samples
 L-200 Freeze Dryer Buchi Freeze drying samples
 CombiFlash® Rf Automated Flash Chromatography System (3) Teledyne Isco Purification of organic compounds in normal-phase or reversed phase separations
 1st Combiflash Next Gen 300+ Automated Flash Chromatography System (3) Teledyne Isco Purification of organic compounds in normal-phase or reversed phase separations
 Explorer 72-position Automated Research Microwave Reactor Discover-SP (2) CEM Utilizes microwave energy (single-mode, focused technology) to accelerate organic reactions
 400 MHz NMR (with multiple probes and autosampler) Varian Routine 1H and 13C NMR, 1D and 2D spectra/[ESOP facility – co-located with CICBDD]