Dundee, Tuesday 9th May 2017
The Phenomics Discovery Initiative (PDi), a unique collaboration between the pharmaceutical industry and academia, has unveiled its first series of novel phenotypic assays. The assays are under development within the labs of the National Phenotypic Screening Centre (NPSC) – a collaboration between the Universities of Dundee, Edinburgh and Oxford - and are designed to identify new molecules with pharmacological activity in respiratory, oncology, immunology and cellular stress indications.
The consortium is building a strong portfolio of novel and complex cell-based assays, sourced from the global academic community. The NPSC will screen high-quality compound collections from industry against these validated assays, providing new therapeutic starting points with higher chances of success than those derived from traditional biochemical screening approaches.
Professor Neil Carragher, of the University of Edinburgh and Chief Scientific Officer for the PDi, said, “We are excited to work with our academic and industry collaborators to translate cutting-edge scientific breakthroughs into assays that can generate new knowledge on disease pathways and deliver starting points for new therapies. We are confident that the assays we have selected for screening will be useful to our industry partners in generating new leads for drug discovery programmes.”
Dr Paul Andrews, Director of Operations for the NPSC at the University of Dundee, said: “We have teams of highly talented biologists and screening scientists in the three labs busily working on these assays and we are making great progress. The interactions with our industry partner are highly productive and also very rewarding to our own scientists and those from the academic labs we work with. By spending time focussing on recapitulating aspects of human physiology, we hope to accelerate the development of more effective drugs.”
To enable broad scientific participation in the work of the PDi, NPSC created an online assay submission portal, which is easy to use and can be accessed globally. After six months of operation, the NPSC has attracted over 100 proposals, 14 per cent of which came from outside of the UK.
Assay proposals representing major areas of unmet therapeutic need are well represented with 22 per cent of projects being relevant to oncology, 12 per cent to CNS diseases, 9 per cent to gastrointestinal disease, and 9 per cent to immunology. Respiratory, cardiovascular, metabolic and rare diseases are also represented. The portal remains open for assay submissions: https://npsc.awardsplatform.com
The following six assays are currently being prioritised for compound library screening:
1. A complex human brochoepithelial cell (HBEC) assay, with an air-liquid interface mimicking the real situation in the lung, will be used to screen for novel anti-virals in common respiratory diseases.
2. Manipulation of immune function is becoming increasingly recognized as an effective method to combat disease, particularly in autoimmunity and cancer treatment. A selected assay submitted by Professor Doreen Cantrell’s laboratory at the University of Dundee will aim to identify novel ways of boosting cancer immunotherapies by reactivating “exhausted” T cells.
3. Drugs that control Endoplasmic Reticulum (ER) stress will be applied to a range of protein misfolding disorders known as serpinopathies. This was the rationale for PDi selecting King’s College London, Dr. Tamir Rashid’s assay, which targets this cellular mechanism as a therapy for alpha-1 antitrypsin deficiency in liver cells.
4. Controlling cancer cell “stemness” could have a significant impact in a range of oncology treatments, which is why PDi selected an assay submitted by Dr. Steven Pollard from the MRC Centre for Regenerative Medicine at University of Edinburgh aimed at manipulating cancer cell self-renewal in the brain cancer glioblastoma, a highly refractory cancer that has an extremely poor survival rate.
5. Senescent cells and the factors they produce are detrimental to the health and function of aging tissues. PDi selected an assay submitted by Juan Carlos-Acosta from the MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, which aims to identify novel approaches that either bypass cellular senescence or selectively target senescent cells (e.g. senolytics) which may reduce age-related tissue dysfunction (e.g. in atherosclerosis, neurodegeneration, osteoporosis, type II diabetes, cancer) and prolong healthy lifespan.
6. Targeting signalling in cell proliferation as an approach in cancer treatment is being addressed with an assay that aims to influence the so-called “Hippo” pathway that was submitted by Dr. Carsten Hansen from the MRC Centre for Inflammation Research, University of Edinburgh.
The selected assays encompass the latest advances in primary, patient-derived and human induced Pluripotent Stem Cell (hiPSC) model systems combined with CRISPR/Cas9 gene editing and novel imaging reagent tools. The cutting-edge assay development and screening technologies available at NPSC allow multi-parametric high-content analysis to be performed to industry scale and standards on complex cellular models such as patient tissue, hiPSC, organoids and multicellular co-cultures. Screened against large annotated and diverse chemical libraries, these assays generate pre-competitive data that is high-quality, physiologically relevant, and a potential start-point of new therapies and new drug targets.
About the Phenomics Discovery Initiative
Launched in 2016, the Phenomics Discovery Initiative (PDi) is a public-private consortium that aims to enhance translation of phenotypic biology into novel therapeutics for patients. Founding members are Janssen Pharmaceutica NV, part of the Pharmaceutical Companies of Johnson & Johnson, and the Universities of Dundee, Edinburgh and Oxford. Learn more at http://npsc.ac.uk/pdi
About the National Phenotypic Screening Centre
NPSC is a world-class facility for automated, high content, phenotypic screening. The goal of the NPSC is to bring advances in industrial drug screening capabilities to academic investigators. NPSC is a partnership between the Universities of Dundee, Edinburgh and Oxford. The project was established with an £8M infrastructure award from the Scottish Funding Council to the Scottish Universities Life Science Alliance (SULSA). NPSC operates as an open centre and aims to collaborate globally to develop the physiologically-relevant assays from biologists who are keen to achieve impact by seeing their best research ideas translated from the lab into the drug discovery pipeline. Learn more at www.npsc.ac.uk
About the University of Dundee – School of Life Sciences
The University of Dundee is the top ranked University in the UK for biological sciences, according to the 2014 Research Excellence Framework. With more than 900 scientists, research students and support staff from 61 countries and external funding in excess of £50 million per annum, the School of Life Sciences at the University of Dundee is one of the largest and most productive Life Sciences research institutes in Europe. The University of Dundee is the central hub for a multi-million-pound biotechnology sector in the east of Scotland, which now accounts for 16% of the local economy. Learn more at www.lifesci.dundee.ac.uk
About the University of Oxford – Nuffield Department of Medicine
The University of Oxford has been top rated for Medicine (Clinical, Pre-clinical and Health subjects) for the last 5 consecutive years and hosts one of the largest groupings of biomedical scientists in the university sector. The Nuffield Department of Medicine (NDM) is a large multi-disciplinary department that links high quality clinical research with medical application. The underpinning motivation behind all research carried out by NDM is the pursuit of academic excellence and the positive impact of research on the health and wellbeing of the global community. NDM employs around 1000 scientific research staff within the UK, and a further 1,500 staff overseas. Its researchers also contribute to the teaching of 450 medical students within Oxford University's Clinical School, further solidifying its bench to bedside philosophy. Learn more at http://www.ndm.ox.ac.uk
About the University of Edinburgh – Schools of Medicine and Biological Sciences
The University of Edinburgh is rated in the world’s top 15 for medicine, biology, and computer science, with over 3000 scientists working in these areas alone. It offers the ideal platform for understanding disease and then designing and developing new drugs to help patients.
Work at the Edinburgh hub will be carried out at the Edinburgh Phenotypic Assay Centre (EPAC) a joint initiative between Edinburgh’s renowned Schools of Medicine and Biological Sciences spear-headed by Professors Neil Carragher, Margaret Frame and David Gray. Learn more at http://www.ed.ac.uk/medicine-vet-medicine/edinburgh-medical-school