Environment

UPDDI Core Facilities and Equipment

Discovery Technology

The UPDDI occupies a total of 7,412 sq. ft. of laboratory space on the 4th floor of the Pittsburgh Technology Center:

  • Three individual wet laboratories containing facilities to propagate a wide variety of mammalian, insect and yeast
    • A dedicated Microphysiology laboratory
    • A dedicated High Content Imaging laboratory
    • A dedicated High Content Screening and High Throughput Screening facility
    • A chemicals/preparation room for reagent preparation and HTS consumables storage
  • Automated liquid handling systems:
    • Two bulk liquid dispensers
    • Four compound dilution and transfer systems
  • Detection instruments enabling running every kind of assay:
    • Multimode plate readers
    • Absorbance
    • Luminescence
    • Fluorescence intensity, time-resolved, fluorescence, fluorescence polarization
    • Automated high-content microscope imaging platforms
    • Two Etaluma automated, incubated microscopes for online, long term monitoring of live cells in microfluidic devices
    • Two Olympus IX50 microscopes equipped with epifluorescence and monochrome/color CCD cameras (video capable)

Analysis of large and complex data sets is handled through a variety of LIMS and HTS/HCS analysis software on data servers hosted at UPitt’s secure, state of the art Network Operations Center (NOC) with 24/7 monitoring and redundant power and cooling systems. Active data are backed up daily and static data archived semiannually. The servers are connected via a state-of-the-art network.

 

       

The BioSystics Analytics Platform (EveAnalyticsTM) is a unique online resource that was developed at the UPDDI that manages, analyzes, shares and computationally models complex data sets from in vitro experimental models, animal models and human clinical data creating actionable knowledge and predicting biological outcomes.  BioSystics, Inc. was spun out if the UPDDI and merged with Nortis, Inc. to form Numa BioSciences who maintains the BioSystics-AP as a shared data resource for microphysiology systems data from remote laboratories, along with locally generated data, as well as a commercial software system that can be installed on-site when working with proprietary data.

 

Chemistry/Medicinal Chemistry Facility

UPDDI has access to chemistry and medicinal chemistry laboratories through the University of Pittsburgh School of Pharmacy. The available equipment and facilities allow UPDDI access to non-GLP pharmaceutically relevant compounds from milligram to multi-gram scale.

Computational Biology and Chemistry

An important aspect of the new vision for drug discovery at the UPDDI is the permeation of computational tools for integrating omics data, inferring disease mechanisms, identifying targets, analyzing drug-target interactions and developing strategies to advance novel chemical series. In addition to the UPDDI’s internal resources, we have access to computational facilities in the Department of Computational and Systems Biology (DCSB), the Center for Research Computing (CRC), and the Pittsburgh Supercomputing Center (PSC)

The available DCSB hardware includes a large number of computers to conduct its research in an efficient and effective manner.  These computers include high-end workstations in the offices and a number of rack-mounted Linux clusters at the NOC.  The clusters are for running complex simulations, models, and computations that take a long time to complete or can run in parallel across nodes. 

The CRC maintains different types of hardware for various advanced computing needs. 

The PSC houses three supercomputers, including Bridges and Anton, a dedicated molecular dynamics supercomputer built by D. E. Shaw Research. 

Through these resources, our researchers have access to a wide range of free and licensed scientific software, including NAMD, GROMACS, Amber, Gaussian, Matlab and tools from OpenEye and Schrodinger. The Health Sciences Library System additionally provides access to biomedical analysis tools, such as Qiagen’s CLC and Ingenuity suites. 

 

Zebrafish Facility

The University of Pittsburgh School of Medicine’s aquatics research facility is one of the largest in the world. It occupies 4,600 sq. ft. of floor space on the 5th floor of the BST3, holds 11,000 fish tanks in its main system and 480 tanks in its quarantine system, and can maintain 500,000 adult zebrafish. The main system consists of two independent 5,500-tank systems with automated water filtration. Three independent light control chambers enable alternative photoperiods. Automated monitoring equipment regulates pH, conductivity, and temperature of the water in the system. A 282 net sq. ft. injection room holds six injection apparatus within the facility. This allows up to six researchers to simultaneously perform microinjection on zebrafish embryos, an important aspect in the establishment of transgenic lines. In addition, there are seven fluorescent and bright-field, high-end, stereomicroscopes for visualizing and documenting transgenic reporter expression, and for screening chemically treated embryos. All veterinary and husbandry care is provided by veterinarians and supporting personnel in the Division of Laboratory Animal Resources (DLAR), which is overseen by the University Institutional Animal Care and Use Committee, and complies with the Animal Welfare Act, NIH policies, and all other applicable federal, state, and local laws. Animal facilities at the University of Pittsburgh have been fully accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC) since 1971, and the International Association for the Assessment and Accreditation of Laboratory Animal Care.

 

Preclinical Resources

The combined resources available for preclinical studies are listed below.

In vitro

The equipment available for in vitro/ex vivo work includes: analytical balances, microcentrifuges, table top centrifuges, (fluorescent) microscopes, laminar flow hoods, CO2 incubators, shaking water baths, liquid nitrogen storage for cells, refrigerators, freezers, gel electrophoresis, microplate readers, pH meters, Z1 Coulter counter, light box, and access to the shared use equipment within Hillman Cancer Center which includes: liquid scintillation counters, gamma counters, X-ray film developers, Molecular Dynamics Densitometer, ultracentrifuges, autoclaving and glass washing services, Tecan Safire and Licor Odyssey, etc.

In vivo

The Division of Laboratory Animal Resources University of Pittsburgh maintains the animal care facilities at the Hillman Cancer Center, Basic Research Pavilion, and is fully accredited by the American Association for Accreditation of Laboratory Animal Care. Within the Central Animal Facility, Dr. Beumer has a dedicated laboratory (G11.8) and fully equipped animal procedure room (G11.9), as well as an animal housing room (G11.28a) capable of handling 1500 rodents at any time.

Analytical

Analytical equipment available for preclinical research includes a Perkin-Elmer model AAnalyst 600 Atomic Absorption spectrometer, two regular HPLC UV systems with dual wavelength, photo-diode-array, fluorescence detector, and one HPLC system with UV and radioactivity detection, four Waters QuattroMicro triple stage mass spectrometers, and two Applied Biosystems 4000 triple-quadrupoles. All mass spectrometric detectors are supplied with high purity nitrogen generated by a Parker Balston nitrogen generator model 75-880, supplied with compressed air by a Copto air-compressor located in the basement of Hillman Cancer Center.

         
         

Major equipment at the UPDDI

  • 7 tissue culture hoods
  • 14 CO2tissue culture incubators
  • Multiple perfusion pumps with capabilities to run up to 80 microphysiological devices at a time
  • Multimode plate readers
    • Molecular Devices SpectraMax M5 and M5E
    • FlexStation 3 kinetic reader
    • Perkin Elmer EnVision
  • High content imaging platforms
    • Perkin-Elmer Opera Phenix Plus high resolution 3D imaging system with dual cameras, FLEX 750 robotic plate::handler™, and liquid handling capabilities
    • Perkin-Elmer Operetta CLS System, both with Harmony software for image acquisition and analysis, and the Columbus database software for image processing and data management
    • GE Healthcare IN Cell 6000 laser based confocal system with environmental control for live cell analysis
    • GE Heathcare IN Cell 2200 wide field HCS system
    • ArrayScan VTi wide-field system integrated with a Caliper Twister II plate handler
  • Microscopes
    • Two Olympus IX50 microscopes equipped with epifluorescence and monochrome/color CCD cameras (video capable)
    • Two Leica DM IL inverted phase contrast microscopes
    • Two cell culture microscopes
  • Robotic liquid handling systems for bulk delivery of reagents or cells
    • Thermo Scientific Multidrop Combi
    • Biotek Microflo
  • Automated compound dilution and transfer systems
    • Janus MDT
    • Velocity 11 Bravo
  • BioTek plate washer for washing cells in 96- and 384-well plates.

List of UPDDI analysis software

  • Two IDBS ActivityBase™ LIMS with Chemistry Selection Assistants, and Protocol Transfer Assistants seats
  • Two IDBS SARview seats
  • Three licenses for the IN Cell Investigator HCS software
  • Two Cellomics platinum packages of Bio-Application image analysis algorithms
  • Four vHCS™ Discovery Toolbox licenses and four vHCS™ View licenses
  • 6 Spotfire® data visualization licenses
  • MetaXpress and Acuity site licenses
  • A Definiens image intelligence suite for custom image analysis including one developer, one architect, and two Cellenger licenses

  List of UPDDI servers

The information systems are comprised of Twenty-one servers (both physical and virtual), including:

  • A scalable Dell Compellent Storage Center SC4020 solution as the central data warehouse with 122 TB formatted storage, upgradeable to 408 TB without any major configuration change
  • Two Dell PowerEdge (PE) R720 servers with 128 GB memory, dual Intel Xeon E5 processors and 12 TB local storage for virtualization of workstations and servers
  • A PE R720 server with 16 GB memory, dual Intel Xeon E5 processors and 25 TB storage to host the GE IN Cell Miner database A VMWare virtual server hosting an Oracle Database and IDBS ActivityBaseÔ LIMS server
  • A VMWare virtual server hosting MS SQLServer 2008 to house the ArrayScan® VTI and ArrayScan II Cellomics StoreÔ databases
  • A VMWare virtual server hosting MS-SQLServer 2008 to house the Molecular Devices MDCStore database
  • A high-performance Dell 2950 application server with four analysis engines and two high-speed dual quad-core CPUs to house the Definiens image intelligence suite.
  • A Dell PE R730 server with dual 2.1 GHz Intel Xeon processors, 32 GB memory, and 32 TB of disk space is replicated and  dedicated to the MPS-Db.

UPDDI also has a state-of-the-art VMware Cluster, with VMware VCenter running VMware vSphere 6 (ESXi 6.70) using two Dell PowerEdge R440, with Xeon 2.60 GHzCPUs, 64 GB of RAM as compute nodes, to host Virtual servers, providing high availability, redundancy and failover.