Phenomics Discovery initiative launched

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.

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. 

Professor Sir Peter Ratcliffe, Director of the Target Discovery Institute at Oxford and co-founder of the Phenomics Discovery initiative

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.'