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
Biocentury, a leading provider of value-added information, analysis and data for the biotech and pharma industries, has just published and article highlighting a comeback of phenotypic screening in drug discovery, deemed the "Phenomics Phenomenon", ....and NPSC is a part of it!
In the article Michael Leviten interviewed industry leaders from Johnson and Johnson, Novartis, Perlara, Recursion Pharmaceuticals, Servier, Teleos, and Vertex Pharmaceuticals, who expressed thier opinion that the current prefered approach in early drug discovery that combines genetic screens with traget-based approaches, is not delivering enough results in the clinic.
Michael also interviewed leaders from academia, including our COO Dr Paul Andrews, who are adopting the new technologies that enable phenotypic screening to be fit for translating novel biology into drug discovery. Paul exposed the main reasons for the adoption of phenotypic screening in drug discovery, which includes physiological relevance of the assays, and higher sucess rates in translation to the clinic. New phenomics technologies, which are available at the NPSC, allow complex models of human disease, such as iPS cells, co-cultures, organoids and patient tissue, to be screened against large compound libraries at the same time as multiparapetric data is measured (more than a 1,000 data points can be measured simulateously). This means that phenotipyc screening is now, more than ever, relevant to modern drug discovery.
Research teams based the Universities of Dundee and Edinburgh are looking to partner with the pharmaceutical industry to better understand the biological processes that could allow the development of new drugs to support tissue regeneration or repair. Monday 6th March 2017 - PRESS RELEASE FROM University of Dundee, the University of Edinburgh and the Medical Research Council
The National Phenotypic Screening Centre (NPSC) at the University of Dundee and the Medical Research Council (MRC) Centre for Regenerative Medicine (CRM) at the University of Edinburgh have signed a memorandum of understanding that commits them to work more closely together as they strive to translate novel biological discoveries into new stem cell therapies.
Regenerative medicine therapies to treat a range of debilitating diseases (including blindness, liver disease, Parkinson’s disease, arthritis and many others) are actively being developed around the world. Many of them are and are based on one of two approaches: implantation of stem-cell-derived cells or the use of drugs to selectively activate and mobilise the body’s own stem cells in order to replace damaged or diseased tissues. Understanding the stem cells in tissues and their supporting environment (the stem cell “niche”) is critical to both approaches.
The UK Regenerative Medicine Platform funded “Engineering and exploiting the stem cell niche” Hub, led by the MRC Centre for Regenerative Medicine (CRM) at the University of Edinburgh, is dedicated to further understanding of the biology of stem cell niches and to exploit this knowledge therapeutically to improve organ regeneration through endogenous repair and cell transplantation
Finding new drugs which can activate endogenous regenerative pathways requires the development of cell-based assays that are able to reproduce the complex behaviour (the “phenotype”) of the cells and tissues in patients. The National Phenotypic Screening Centre (NPSC) specialises in developing such complex assays so they can be systematically screened using large libraries of drug-like molecules to uncover agents that can alter cell and tissue behaviour.
Close collaboration between the two centres, which together represent government investment amounting to around £35M, will allow novel biological discoveries from CRM to benefit from the expertise and industrial drug screening infrastructure provided by the NPSC, leading to the start-points for new therapies. An in-depth understanding of cell and tissue function will facilitate the search to find molecules that improve key tissue regeneration processes that could eventually be used as drugs for regenerative repair.
Professor Stuart Forbes, Director of the Centre for Regenerative Medicine and co-director of the Niche Hub, said, “Stem cell medicine is coming of age, this is a great opportunity for Scottish Universities to partner with industry to ensure we can translate excellent science to new therapies that can help patients with chronic disease.”
Dr Paul Andrews, Director of Operations at the NPSC, said, “We are very excited to be able to sign this agreement which will help cement our growing relationship with the excellent scientists that are within the MRC Centre for Regenerative Medicine and the wider UK Regenerative Medicine Hub network.”
UKRMP Director Dr Rob Buckle said, “This MOU between the Niche Hub and NPSC extends the growth of the UKRMP by encouraging further interactions with the wider UK research community which will help to open up new opportunities and approaches to help deliver the great promise of regenerative medicine.”
The National Phenotypic Screening Centre (NPSC) was set up by the Scottish Universities Life Science Alliance (SULSA) with a £8M capital funding from the Scottish Government to provide state-of-the-art capabilities in the development and screening of physiologically-relevant assays for academia and allow close collaboration with industry. The main facility is in newly-refurbished labs within the School of Life Sciences at the University of Dundee (working closely with the Edinburgh Phenotypic Assay Centre at the University of Edinburgh and a sister screening lab at the Target Discovery Institute at the University of Oxford). The NPSC has an interdisciplinary group of scientists and engineers using world-class high throughput imaging platforms that can be applied to human, animal, and plant health challenges. www.npsc.ac.uk.
About the MRC Centre for Regenerative Medicine (CRM)
The MRC Centre for Regenerative Medicine (CRM) is a world leading research centre based at the University of Edinburgh. Scientists and clinicians at the CRM study stem cells, disease and tissue repair to advance human health. CRM is housed within the Scottish Centre for Regenerative Medicine building, on the Edinburgh bioQuarter site shared by the Royal Infirmary of Edinburgh and the University's Teaching and Clinical Research facilities. With state-of-the-art facilities and a 230+ team of scientists and clinicians, CRM is positioned uniquely to translate scientific knowledge to industry and the clinic. Research at CRM is aimed at developing new treatments for major diseases including cancer, heart disease, liver failure, diabetes, and degenerative diseases such as multiple sclerosis and Parkinson's. CRM is led by Centre Director Prof Stuart Forbes. www.crm.ed.ac.uk
About the UKRMP
The UK Regenerative Medicine Platform (UKRMP) is a £25M investment by the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC) and the Medical Research Council (MRC). The UKRMP addresses the technical and scientific challenges associated with translating promising scientific discoveries in this area towards clinical impact, and seeks to provide a world-leading programme to promote the development of regenerative therapies. Central to the Platform are five interdisciplinary and complementary research Hubs with the necessary critical mass to address key translational challenges and provide new tools, protocols and resources with broad applicability that can be utilised by other UK research groups in academia and industry. In addition, five Disease/Systems focused research programmes have been funded, which that link to or exploit aspects of the science being progressed through the Hubs. www.ukrmp.org.uk
About the UK Regenerative Medicine Platform (UKRMP) Niche Hub
The UKRMP Engineering and Exploiting the Stem Cell Niche Hub is one of five research hubs funded by a grant from the UK Regenerative Medicine Platform, which receives funding from the MRC, BBSRC and EPSRC and is led by the University of Edinburgh. Niche Hub research is focused on understanding the signals to stimulate cartilage, liver, and neural tissue repair and on developing tools and technologies for real-time analysis of the regenerating tissue. The Niche Hub is composed of 8 institutional members (Universities of Edinburgh, Liverpool, Cambridge, Imperial College, Keele, King’s College, Manchester and Strathclyde) with 21 principal investigators (PIs) and 10 Post-Doctoral Research Assistants. The focus of the Niche Hub is to exploit therapeutically our understanding of the biology of stem cell niches. The Niche Hub uses this knowledge to optimise the growth and differentiation of stem cells and improve organ regeneration through endogenous repair and cell transplantation.
NPSC's phenotypic screening platform is at the heart of efforts to develop a male pill.
The Bill and Melinda Gates Foundation have pledged $600,000 towards finding novel approaches to male birth control, which has been awarded to several laboratories worldwide. Different approches are being used to address the challenge, including genetic approaches to identify genes that might be good contraceptive targets, induced pluripotent stem cell approaches to find a better human model for male-contraceptive drug screening, and phenotypic approaches to identify agents that act on sperm function and fertility. NPSC is contributing to this this effort with high throughput biology and novel multiparametric phenotypic screening methods. High content imaging technology will be used to track sperm movement and to capture the “acrosome reaction,” when sperm shed a cap-like structure before penetrating an egg. A drug able to immobilize sperm, or block that reaction, could be a starting point for an effective contraceptive.
Thursday 8th December 2016 - 13.00 to 14.00
University of Glasgow - Wolfson Medical School
Gannochy Lecture Theatre, Room 248 Wolfson Medical School Building,University Place, Gilmorehill Campus, Glasgow G12 8QQ
Thursday 8th December 2016 - 15.00 to 16.00
University of Glasgow - Wolfson Wohl Cancer Research Centre
Seminar Room, Wolfson Wohl Cancer Research Centre, Garscube Estate, Switchback Road, Bearsden, G61 1QH
Friday 9th December 2016 - 12.00 to 13.00
University of Aberdeen - Level 5 conference room - Institute for Medical Sciences (IMS), Forrester Hill Campus, Aberdeen AB25 2ZD
We are looking for biologists and clinicians with phenotypic assays or assay-concepts, that are interested in translating their research. We offer the opportunity to get these assays screened to industry standards against best-in-class small molecule compound libraries. In this seminar we will present the opportunities for assay development and phenotypic screening that are available at NPSC.
NPSC is a world-class facility for phenotypic screening run by an interdisciplinary team of scientists and engineers who collaborate to advance the use of complex biology and to drive innovation. NPSC was set up to complement the activities of the target-based screening centres, taking a more holistic approach to understanding disease at the cellular and tissue level. Focused on using “high-content” image-based approaches to hit discovery, initial emphasis will be on tackling complex, multi-faceted diseases, employing the most physiologically relevant assays possible.
Screens are performed using high quality compound collections to generate either new understanding of disease pathology and toolbox reagents for further academic use, or validated chemical start points for pre-clinical drug development. Phenotypic assay development will take place as a joint effort between the NPSC and the academic lab or clinician, thereby bridging the gap between early stage data and an industry-standard assay.
In addition to being accessible via existing funding routes, the NPSC has established the Phenomics Discovery Initiative (PDi), a public-private partnership between industrial pharmaceutical companies and NPSC. PDi seeks to identify, develop, screen and validate innovative phenotypic assays that are relevant to human disease. PDi phenotypic assays are recruited from proposals made by academics, clinicians and SMEs. Selected proposals are screened free of charge.
Phenotypic screening embraces the complexity of organisms, tissues and cells in order to identify bioactive agents such as small molecules and antibodies. Rather than being focused on biochemical assays on an isolated target molecule, it relies on a more holistic and empirical approach often using live cell assay systems. When integrated early in the drug discovery process, phenotypic screening hits can progress faster as they already act in the correct context, improving success rates for lead selection/optimization, and reducing failure in phase II and III due to poor safety and low efficacy.
The project will enable a unique collaboration bringing together expertise at Dundee in male fertility and drug discovery to help identify possible new male contraceptive drugs.
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