IBT High Throughput Research and Screening Center-Houston, TX

A unique resource providing researchers from Texas A&M and the Texas Medical Center with access to state-of-the-art tools to support the discovery of new drugs and new treatments for some of the most devastating diseases of our time. The Combinatorial Drug Discovery Program resides in the Texas A&M Health Science Center’s Institute of Biosciences and Technology. This core provides industry standard high throughput screening and microscopy capabilities to scientists carrying out chemical and genomic biochemical and drug discovery research. The core supports investigators from all of the institutions in and around the Houston/Galveston region and with pharmaceutical and biotechnology partners. The core provides many benefits, such as access to an automated infrastructure that is capable of supporting both biochemical and cell-based screens. The core also provides ready access to a collection of nearly 60,000 drugs, investigational agents and small molecules. Our collections of test agents include current FDA-approved clinical candidates and off-patent drugs exhibiting the ‘drug-like’ qualities of acceptable solubility, desirable ADME/toxicology properties and adequate bioavailability. These properties are important for rapid advancement of new agents into successful preclinical and clinical trials by discovering new therapeutic vulnerabilities alone or in combinations. We also have collections of mechanistically annotated informer sets that are pathway specific modulators for studying mechanism of action. The core also has collections of natural products and diverse sets of small molecules that can be interrogated for new target discovery. The greatest benefit of the core; however, is its fulltime professional staff. The screening team is composed of highly experienced biologists, biochemists, pharmacologists and bio-informaticians with pharmaceutical industry and academic experience. Each project is individually evaluated and a team of scientists from the core is created to fit the specific needs of the project from assay development through primary, secondary and orthogonal screening. The team is committed to providing an integrated and highly collaborative program with every investigator.

Equipment:

• Multimode microplate reader: BioTek Synergy Neo2 with plates loader
• Labcyte Echo 550: acoustic dispenser integrated into an Access workstation with a Cytomat cell culture incubator and Thermo Scientific Multidrop Combi.
• Tecan Evo 200 workstation: capable of 96, 384 tips transfer as well as pintools, integrated with Tecan multimode readers M1000pro and two 222-plates capacity Liconic incubators, RT and humidity controlled cell culture.
• Two dual arm Beckman-Coulter Biomek FXP platforms, Beckman NX P. Both the Tecan Evo200 and Beckman FXP workstations have both a 96-channel and variable spanning 8-channel pipettor as well as pin tool capabilities. The peripherals include a temperature and humidity controlled cell culture incubators and consumables storage system from Cytomat and Liconic, BioTek ELx405 and DTX.
• Tecan Hydrospeed microplate washer and Multidrop Combi system with stackers.
• Several Multidrop Combi integrated to our automation workstations as well as stand alone

All cell based growth, viability and multiplexed high-content imaging studies are performed using our primary screen platform in conjunction with our imaging systems which provide high-performance laser-based, confocal, high-content analysis for 2D, 3D, and spheroids cultures

• GE Healthcare IN Cell Analyzer 6000: a self-contained unit with an integrated Kindex plate handler, 90 plates capacity from Process Analysis & Automation Ltd., United Kingdom. This system is capable of collecting images from slides to 1536well plates and more that 200,000 wells per day, from 4x – 40x air lenses (field-of-view at 10×: 2.78 mm2) and is capable of automatically switching from low to high magnification without additional system setup.
• Molecular Devices ImageXpress: Micro confocal microscopes: is integrated with a Cytomat cell culture incubator for continuous live cell imaging 24hrs a day. The microscope has a large CMOS camera and is capable of 5 colors fluorescence imaging with 2x – 40x air lenses (field-of-view at 10×: 1.96 mm2). The platform is capable of imaging from slides to 1536well plates and is capable of collecting images from more than 200,000 wells per day.

In addition to expertise, we have built significant computational infrastructure to handle the large volume of data produced in phenotypic screening. Key computations systems include: A dedicated image analysis server with 40 logical processors, 192 GB of RAM, GPU processor, and 20 Tb of local storage; 4 peripheral workstations each with at least 10 logical processors, 64 GB of RAM, and a GPU; A centralized data server with a storage capacity of 100Tb. All computational resources can be utilized as a single unit using server management and task automation tools in Pipeline Pilot.

Statistical services

• Assay design optimization
• Assay performance evaluation
• Data normalization and integration
• Exploratory analysis
• Development of automated classifiers using state-of-art machine learning techniques

Image analysis services

• Development of custom image analysis
• Upscaling of established protocols
• Experience with monolayers, organoids, spheroids, and time lapse data

Bio- and Chemi-informatics support

• Chemical space profiling
• Quantitative structure activity relationship
• Biomarker discovery
• Knowledge base mining
• High dimensional data embedding

Key software and programming languages

• Pipeline Pilot from Biovia
• Matlab from Mathworks
• Prism from Graphpad
• R programming language
• Python programming language
• IN Cell Developer from GE Life Sciences
• MetaXpress from Molecular Devices
• ImageJ from NIHs
• CellProfiler from the Broad Institute
• Excel from Microsoft

Key Computational infrastructure

• Dell T630 server with dual Xenon processors, 192 GB RAM
• 4 peripheral workstations each with at least 10 core Xenon processor, 64 GB RAM
• Centralized 100 Tb data storage server
• Server integration software