Drug discovery
World-class drug discovery platforms with a track record in successfully translating drug discovery projects from target identification through to clinical evaluation
Edinburgh Drug Discovery
Based in: Institute for Genetics and Cancer (IGC)
Edinburgh Drug Discovery's specialities encompass biomarker discovery, target discovery, target validation, drug design and development, phenotypic screening and clinical research. The staff combines a high degree of skill in various aspects of drug discovery research with creativity and use of state-of-the-art instrumentation and facilities to deliver results.
Small molecule synthesis and medicinal chemistry
Facility manager/ lead contact: Dr Asier Unciti-Broceta
The facility's medicinal chemists are experts in the design and synthesis of bioactive small molecules. They specialise in ligand-based drug design and strategically combine this with phenotypic screening to produce highly potent, exquisitely selective compounds with a high degree of drug-like character.
Target-based screening, protein expression and drug metabolism and pharmacokinetics
Facility manager/ lead contact: Dr Scott Webster
The facility's core drug development team are skilled in the use of a variety of methods for the production of recombinant protein for target-based high throughput drug screening.
The team is proficient in achieving expression of recombinant target protein in a variety of cell types for cell-based assays and has experience in developing bespoke target-based screening assays in high throughput format using technologies such as HTRF, FP and LC-MS/MS. A particular area of expertise is in enzyme targets where the team has advanced several small molecule inhibitors to candidate selection and onto clinical development.
With its suite of drug metabolism and pharmacokinetic assays, including rodent-based assessment of the pharmacokinetics and pharmacodynamics of compounds, the team can quickly deliver results contributing to optimisation of lead compounds.
Cellular pharmacology and phenotypic profiling
Facility manager/ lead contact: Professor Neil Carragher
Edinburgh Drug Discovery also develops novel cell-based assays across disease areas and implement robust high-throughput/high-content phenotypic screens. These screens couple multiparametric high content imaging with artificial intelligence/machine learning approaches to deliver novel mechanistic insights and highly quantifiable results.
Their high-throughput screening efforts are ably supported by a range of high throughput liquid handling and microscopy instrumentation as well as several high quality compound libraries of novel chemical entities, reference compounds and FDA approved drugs.
High-throughput, antibody-based proteomics (reverse phase protein microarrays) and NanoString platforms enable rapid profiling of compound mechanism of action as well as off-target activities and support lead compound optimisation.
Edinburgh Drug Discovery website
High Content Screening Facility
Based in: Centre for Regenerative Medicine (CRM)
Facility manager/ lead contact: Dr Justyna Cholewa-Waclaw
High Content Screening Facility provides equipment, expertise and support for development of semi-automated workflow to increase assay throughput and screening. The facility is equipped in state-of-art high content imaging platform - Opera Phenix Plus - a spinning disk confocal which provides dramatic increase in speed of image acquisition. Opera is capable of imaging thick samples such as organoids and tissue slices, moving the facility towards 3D disease models. This system also allows long-term live imaging with its humidity-, temperature- and CO2-controlled chamber. Moreover, Opera is supported by liquid dispenser for compound addition and robotic arm for high throughput imaging. The facility is also equipped in various types of liquid handlers which allow cell seeding, reagent addition and plate washing for complete assay development workflow. Finally, it provides support for high content image analysis using Perkin Elmer image analysis software - Harmony and server-based Columbus/Image Artist.
High Content Screening Facility website
Host and tumour profiling Unit (HTPU) microarray services
Based in: IGC
Facility manager/ lead contact: Alison Munro and Kenneth Macleod
This service provides protein, antibody and transcriptomic microarray facilities for the analysis of complex signalling pathways and secreted factors across multiple pre-clinical and clinical sample types:
- NanoString nCounter - highly sensitive profiling of hundreds of mRNAs, microRNAs, SNVs, CNVs or protein using colour-coded molecular barcodes to provide a digital count of target molecules. Optimised for difficult sample types including FFPE, tissue and lysate samples.
- Reverse phase protein arrays (RPPA) - a sensitive antibody based proteomic approach enabling simultaneous quantification of multiple proteins and post-translational modifications. The portfolio of antibodies covers key cancer survival, cell cycle and canonical signalling pathways that can be used to profile multiple pathway responses.
- Forward phase antibody microarrays (cytokine arrays) - utilises well-validated capture/detection antibody pairs for the relative quantification of secreted factors associated with inflammation and angiogenesis i.e chemokines/cytokine/adipokines.
These facilities are available to all within the University of Edinburgh, and to external groups through funded collaboration or fee-for-service contract. The NanoString service obtained ACCORD Accreditation in 2021 and can analyse locally sponsored clinical trial samples.
HTPU Microarray Services website
Zebrafish screening facility
Based in: Chancellor's Building
Facility manager/ lead contact: Jason Early
The Centre for Discovery Brain Sciences hosts the UK Zebrafish Screening Facility. The facility is home to a VAST BioImager and LPSampler (Union Biometrica), which together can automatically load and orient zebrafish larvae for imaging with a high speed spinning disk confocal microscope (Zeiss/Yokogawa).
This allow for rapid phenotypic screening of whole zebrafish larvae for chemical or genetic screening applications. The facility also benefits from a Zeiss LSM880 microscope with Airyscan, allowing for super resolution imaging in vivo. Together these two microscopes allow for rapid in vivo chemical screening, with follow up at the sub-cellular level. To further increase the throughput and robustness of our screening assays, the facility has fully automated image processing and analysis for several of our assays, with more to come.
The UK Zebrafish Screening Facility is open to academic or industry collaborators from the UK and internationally.