National Phenotypic Screening Centre (NPSC)

About

NPSC is a world-class phenotypic screening facility run by an interdisciplinary team of scientists and engineers who collaborate to advance the use of complex biology and to drive innovation. High throughput phenotypic screening (often referred to as “high content screening” or HCS) uses quantitative image-based readouts of cell and tissue models to measure the effects of molecular perturbations on cell and/or tissue models of biological systems and functions.  Examples of assays runs in NPSC include:

• Nuclear translocation assays: measurements of transcriptional regulators into nucleus
• Live cell assays: quantitative assays of cell dynamics in response to drug treatments
• Cell Painting: cell organelle labelling to reveal mechanism of action
• Pathway reporters: antibody and fluorescent protein-based reporters of expression for assessing effects of targeted degradation approaches

Examples of cell and tissue models run in NPSC:

• Immortalised and patient-derived cancer cell lines
• Human-derived keratinocytes and germ cells
• Human induced pluripotent stem cells

NPSC’s facilities include all necessary cell and tissue culture, automated liquid and compound handling, plate handling and data acquisition for running large-scale screening assays.  Advanced computational resources (compute cluster, fully backed up data storage, OMERO Plus data management, CellProfiler and R workflows, Jupyter Hub server) are available for data reduction and analysis.

We have a proven record of working with Academics from within the University of Dundee, other universities in the UK and EU and biotech and pharma companies around the world.

Equipment

Microscopes

• Yokogawa CV7000
• GE InCell2200
• Molecular Devices IXM XLS

Functionality

• 1 dual spinning disc confocal, with integrated liquid handling and full environmental control
• 2 fluorescent widefield systems with temperature control - up to 5 channels in parallel
• DIC, Phase-Contrast and brightfield imaging
• 2D/3D/4D imaging, extended focus and deconvolution
• Time-lapse imaging
• Fast acquisition (>100 fps)
• Slide and 6- to 1536-well plate compatible
• 4x-60x magnification objective lenses
• Integrated software for macro programming and on-line cell counting
• Whole well recording
• Transwell imaging
• Hardware and software autofocus
• Plate mapping, Well ID in image metadata

Flow Cytometry

• NovoCyte Advanteon
• Sartorius iQue

Functionality

• FACS tube, 24-, 48-, 96- and 384-well plate compatible
• 3 excitation lasers, 14 fluorescence detection channels
• High dynamic range (>107 intensity levels)
• Detection rate 100,000 events/second

Plate Reader

• Tecan M1000 pro
• PerkinElmer EnSpire

Functionality

• Multimode fast acquisition – luminescence, fluorescence, and absorbance
• Flexible wavelength and bandwidth selection
• Time-resolved fluorescence (TRF, TR-FRET)
• Fluorescence polarisation
• Temperature control up to 42 °C
• Orbital shaking & injection module
• 6- to 1536-well plate
• Liquid injectors

Liquid Handlers

• Agilent Bravo
• Labcyte Echo550/555
• Formulatrix Tempest
• Formulatrix Mantis
• MultiDrop Combi
• Biotek 405LS

Functionality

• Robotic liquid handling platform for tip-based transfers (96- and 384-pipette heads)
• Highly accurate, low volume acoustic (tip-free) liquid transfers with unsurpassed accuracy and reproducibility
• Reagent dispensers for up to 12 reagents, highly accurate to 1 μL (Tempest) or 0.1 μL (Mantis)
• Cell or reagent dispenser
• Plate washer for fast, whole plate washes (dispense and aspirate, ≥50 μL/well)

Automation

• 6-star (Denso)
• 9-star (Staubli)

Functionality

• Interchangeable modules
• Biological Safety Level 2 compatible (9-star)

Funding bodies

• Bill and Melinda Gates Foundation
• European Union – Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806948

People

Publications

Gruber FS, Johnston ZC, Norcross NR, Georgiou I, Wilson C, Read KD, Gilbert IH, Swedlow JR, Martins da Silva S, Barratt CLR. Compounds enhancing human sperm motility identified using a high-throughput phenotypic screening platform. Hum Reprod. 2022 Mar 1;37(3):466-475. doi: 10.1093/humrep/deac007. PMID: 35048946; PMCID: PMC8888995.

Johnston ZC, Gruber FS, Brown SG, Norcross NR, Swedlow J, Gilbert IH, Barratt CLR. High-throughput phenotypic screening of the human spermatozoon. Reproduction. 2021 Dec 27;163(1):R1-R9. doi: 10.1530/REP-21-0372. PMID: 34882578.

Gruber FS, Johnston ZC, Barratt CL, Andrews PD. A phenotypic screening platform utilising human spermatozoa identifies compounds with contraceptive activity. Elife. 2020 Jan 28;9:e51739. doi: 10.7554/eLife.51739. PMID: 31987071; PMCID: PMC7046468.

Franz S. Gruber, Anthony Richardson, Zoe C. Johnston, Zoe C. Johnston, Rachel Myles, Neil R. Norcross, David P. Day, Irene Georgiou, Laura Sesma-Sanz, Caroline Wilson, Kevin D. Read, Sarah Martins da Silva, Christopher L. R. Barratt, Ian H. Gilbert, Jason R. Swedlow. Sperm Toolbox—A selection of small molecules to study human spermatozoa Published: February 20, 2024