Target Discovery Institute
The High Throughput Screening Facility is a major component of theTarget Discovery Institute (or TDI) which is a new research centre initiated by the Nuffield Department of Medicine and the University of Oxford with a mandate to develop new target screening methodologies, investigate disease pathways as a means for identifying 'drug targets' and advance therapeutically relevant targets for drug development.
Podcast created by NDM for the Target Discovery Institute
The Target Discovery Institute (or TDI) is a new research centre initiated by the Nuffield Department of Medicine and the University of Oxford with a mandate to develop new target screening methodologies, investigate disease pathways as a means for identifying 'drug targets' and advance therapeutically relevant targets for drug development. The centre is located on the Churchill Hospital campus at the Wellcome Trust Centre for Human Genetics and brings together the scientific expertise of several university partners including the Nuffield Department of Medicine, the Department of Cardiovascular Medicine, Department of Radiation Oncology and Biology, the Structural Genomics Consortium, the Department of Chemistry and the Oxford branch of the Ludwig Institute for Cancer Research to advance target discovery. In addition, the TDI has fostered close collaborations with pharmaceutical and industrial companies broadening our expertise and linking academic research with industrial processes for drug development.
A major component of the TDI is the high throughput screening facility currently located in The Henry Wellcome Trust Building until the new Target Discovery Institute building is completed in late 2012/early 2013. The facility currently employs two separate Perkin Elmer Janus liquid handling workstations fully integrated with Biotek plate washers and Perkin Elmer FlexDrop reagent dispensers for all of our 96 and 384 microtiter plate liquid handling applications. The liquid handling workstations are housed in two robotics enclosures, one a BigNeat the other from Scanlaf, to ensure a sterile environment is maintained for all cell based HTS.
Additionally, the TDI makes use of several instruments for HTS readouts.
We employ a Perkin Elmer Envision plate reader which has luminescence, fluorescence, fluorescence polarization, time-resolved fluorescence, and absorbance detection capabilities. The Envision is used for all major assay applications including Cellular, Reporter Gene, Enzyme and Quantification Assays.
High content screening is automated image based screening of cells to measure phenotypic changes through external treatment with siRNA or small compounds. These screens are performed in 96 or 384 well plates over the course of several days. Proteins or structures being investigated are detected using fluorescent tags, for example GFP, or by fluorescently labeled antibodies. We utilize a SCARA robot integrated with an InCell 1000 for our high throughput high content screens.
Flow cytometry in HTS uses fluorescent probes which bind to specific cell associated molecules and allows measurements of various phenotypic, biochemical and molecular characteristics of individual cells. The TDI currently utilizes a BD twin laser FACSCalibur with an integrated BD High Throughput Sampler (HTS) for FACS based high throughput screens.
In addition to the HTS equipment, the TDI has several siRNA and small compound libraries available to investigators for high throughput screening. These include ThermoFisher onTarget plus whole genome and custom designed "druggable" siRNA libraries available in both human and mouse species. Our small compound libraries include biologically active, diverse small compound and FDA Approved drug libraries currently totaling several thousand compounds. These are all available for small compound screening.
The aim of the high throughput screening facility at the TDI is to provide research scientists with access to a comprehensive, cost-effective facility capable of running high throughput cell based small compound and RNAi screens as well as biochemical small compound screens.
All high throughput screens run at the TDI are viewed as collaborations between the TDI and the research scientist developing the screen. In most cases, research scientists are strongly encouraged to participate in not only the transfer and optimization of the screen, but its production as well.
We will work closely together during all stages of the screen, from screening optimization and validation to production and output readout, to final data analysis, in order to ensure successful screening project.