Phenomics Discovery Initiative launched
Published On Wed 20 Jan 2016 by Roddy Isles
The Universities of Dundee, Oxford and Edinburgh have announced the formation of the Phenotypic Discovery Initiative (PDi) with Janssen Pharmaceutica N.V. the first industry partner joining the initiative.
A phenotype is one or more observable features or traits that report changes in a biological system or its reaction its environment. Phenotypic screening is the systematic identification of agents (such as small molecules, biological molecules or genetic mutations) that alter a phenotype.
Phenotypic changes are a factor in most diseases, whether it is a cancer cell undergoing uncontrolled cell division, a motor neuron that fails to connect to muscle tissue, or the complex defects seen in the brain of a patient with schizophrenia.
A continuing challenge for innovative drug discovery is to identify and validate novel biological targets which are critical in developing and/or sustaining disease. Despite substantial effort over many years, compounds advanced to development using classical molecular target-based approaches often fail to show the anticipated efficacy in human clinical trials.
Through the PDi, partners will build robust, disease-relevant phenotypic assays with a focus on human-derived systems with the aim of identifying new drug targets and hit molecules. Promising candidates will be followed up for their mechanism of action in the cell in order to further their development into drugs.
By including the complex characteristics of cell and tissues in healthy and diseased samples, high-throughput phenotypic screening offers the possibility of discovering drugs that act through new pathways, as well as novel targets with unique mechanisms. The expectation is that compounds discovered in this manner will have a higher probability of clinical success.
The PDi will provide pre-competitive access to technology, assay methodologies, high-throughput data, materials and know-how. The assays will be used for screens on publicly available small molecules at the three academic sites - Dundee, Oxford and Edinburgh - which form the National Phenotypic Screening Centre (NPSC) hubs. Industry partners gain immediate access to the developed assays to enable internal drug discovery activities, in partnership with the academic collaborators.
The PDi plans to attract additional industry partners and translate novel biology from a global network of academic collaborators. All partners will benefit from these interactions as new industry-academic partnerships are formed first-hand from novel biological research.
Dashyant Dhanak, Global Head of Discovery Sciences, at Janssen R&D, a division of Janssen Pharmaceutica N.V., said, “We are excited to be working with three of the most scientifically outstanding and prestigious UK academic centres. We expect this initiative not only to add depth and state-of-the-art capability to our phenotypic screening activities but also to allow access to the best of ideas and talent in the application of this promising technology.”
Professor Sir Peter Ratcliffe, co-founder of the PDi, who directs Oxford’s Nuffield Department of Clinical Medicine, said, “This is an exciting opportunity to bring some of the UK’s most prestigious academic institutions together with the pharmaceutical industry and change the culture in how we do translational research. We are delighted that Janssen Pharmaceutica N.V should take the lead in building this public-private partnership.“
Edinburgh University’s Professor Neil Carragher, Chief Scientific Officer for the PDi, said “The focus of the PDi consortium will be the development of novel phenotypic assays amenable to high throughput screening, with the goal of identifying new pathways and mechanisms for drug discovery, by employing systems with higher potential for translation into the clinic. The phenotypic screens we will use are more relevant to patients and their disorders.”
The University of Dundee’s Professor Andrew Hopkins, PDi Chairman and co-founder, said, “All the partners involved in the PDi have a strong commitment to improving how we do drug discovery. Our recent investment of £8M ($12M) to build state-of-the-art screening facilities at the National Phenotypic Screening Centre provides an unparalleled platform for the PDi to achieve its mission.”
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.
About phenotypic screening
A phenotype is one or more observable features or traits that report changes in a biological system or its reaction its environment. Simply-put, phenotypic screening is the systematic identification of agents (such as small molecules, biological molecules or genetic mutations) that alter a phenotype.
Phenotypic changes underlay most diseases, whether this is a cancer cell undergoing uncontrolled cell division, a motor neuron that fails to connect to muscle tissue, or the complex defects seen in the brain of a patient with schizophrenia.
Phenotypic screening uses a range of techniques to measure changes in biological systems, the backbone of phenotypic screening relies on exploiting automated, high-content microscopy. High-content screening technologies are used to identify molecules with a particular biological effect in cell-based or tissue-based assays. High content phenotypic profiling allows a systems level approach to drug discovery that embraces the complexity of disease biological. Phenotypic screening approaches show promise in potentially improving success rates of drug development.
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.
About the University of Oxford – Nuffield Department of Medicine
Oxford University 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.
About the University of Edinburgh – Schools of Medicine and Biological Sciences
Edinburgh University 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.
http://www.ed.ac.uk/medicine-vet-medicine/edinburgh-medical-school
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Roddy Isles
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University of Dundee
Nethergate, Dundee, DD1 4HN
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Email: r.isles@dundee.ac.uk