News

Male contraceptive quest boosted by funding from Bill & Melinda Gates Foundation

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The quest of researchers at the University of Dundee to develop a new male contraceptive has been boosted with a grant from the Bill & Melinda Gates Foundation. Researchers say the $900,000-plus award will enable significant progress to be made over the next two years in the discovery and development of the first safe and effective male contraceptive drug. The University of Dundee is uniquely positioned to pursue this project. It combines the internationally recognised expertise in male fertility research in the School of Medicine with world-class robotic high-throughput imaging facilities at the National Phenotypic Screening Centre and the deep knowledge of drug design, synthesis and safety testing present in the Drug Discovery Unit, both within the School of Life Sciences. Chris Barratt, Professor of Reproductive Medicine in the School of Medicine, said, “No effective, reversible and widely available form of contraception has been developed for the male since the condom and, as such, the burden falls largely to the female. “Progress towards a male contraceptive has been slow because this is a highly neglected area of medical research. The Bill & Melinda Gates Foundation has quite rightly recognised the problem and is investing in efforts to remedy the deficit. This is against the backdrop of a world where it is estimated that more than 214 million women in developing countries have an unmet need for contraception. “According to the Guttmacher Institute, this results in 89 million unintended pregnancies and 48 million abortions every year, often pushing women into life choices that increase poverty and pose severe health risks. The development of a drug for the male directly addresses a critical gap in the contraceptive portfolio.” Dr Paul Andrews, Director of Operations in the National Phenotypic Screening Centre (NPSC), said, “It is a significant challenge but, with the first round of funding from the Foundation, we have successfully established the platforms to allow us to screen many thousands of known drugs and new chemical compounds for their ability to interfere with a couple of really important behaviours (or phenotypes) that are essential for fertility. Firstly, their ability to swim up the female reproductive tract and, secondly, a cellular process in the head of the sperm which must happen for the cell to progress towards the egg. Our screening efforts so far have shown such drugs exist. “With this follow-on funding from the Bill & Melinda Gates Foundation our next objective is to continue the hunt and carefully select the most effective molecules that have the right combination of properties that will make them good candidates for further development into a drug that can be safely taken by males. Drug development is a complicated and lengthy process but we aim to deliver one or two small molecule chemical series that fulfil these criteria within two years. “This goal will be an important milestone along the path to a male contraceptive and a prerequisite for further development and clinical evaluation.” The Dundee team was initially funded for one year through the Grand Challenges Explorations initiative, created by the Bill & Melinda Gates Foundation to supports innovative thinkers worldwide to explore ideas that can break the mould in how we solve persistent global health and development challenges. The new award is for $929,585 over two years. Notes to Editors About the National Phenotypic Screening Centre (NPSC) 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 centre was established in 2014 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 with individual researchers and charities as well as with the commercial sector, whether small businesses or large industry leaders, focussing on the development of the best physiologically-relevant assays for a wide range of human conditions or diseases and is tackling some of the major challenges facing society. Learn more at www.npsc.ac.uk About the University of Dundee The University of Dundee is one of the UK’s leading institutes for medical and life sciences research. Dundee was the top rated university in the UK for biological sciences in the most recent Research Excellence Framework. Research intensity is matched by teaching excellence, with a Gold Award in the UK Teaching Excellence Framework, and one of the best student experiences in the UK. Discover more about Dundee at www.dundee.ac.uk or follow us @dundeeuni

Phenomics Discovery Initiative expands portfolio to new disease areas, translating the best biology into novel therapeutics

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Dundee, 6th March 2018

The Phenomics Discovery Initiative (PDi) has expanded its assay portfolio to a total of 11 complex phenotypic assays that are relevant to human pathophysiology in areas of unmet clinical need including neuropsychiatric illnesses, dementia, cancer and respiratory infections.

PDi is a public-private consortium joining the pharmaceutical industry and the National Phenotypic Screening Centre (NPSC). This expansion of its assay portfolio confirms its ability to source and deliver a cutting-edge phenotypic screening pipeline that addresses high-profile disease areas to meet pharmaceutical industry needs for developing novel therapeutics.

Since June 2016, the consortium has demonstrated it can build a strong portfolio of novel and complex cell-based assays that are openly crowdsourced from the global scientific community. Key to the success of the operation is the process of broad project recruitment via a simple application process, combined with agile project selection and collaborative Terms and Conditions (T&Cs) designed to benefit all partners.

PDi relies on top-down and bottom-up approaches for efficient and geographically-extensive project recruitment to create the best programme portfolio. Assays are selected by the PDi scientific committee, balancing selection criteria such as scientific excellence, proximity to disease state, translational potential, commercial relevance and collaboration partner quality.

The NPSC will develop and implement the phenotypic screens against high-quality compound collections from industry to provide new therapeutic starting points with higher chances of clinical efficacy than those derived from traditional biochemical screening approaches.

Professor Neil Carragher, University of Edinburgh and Chief Scientific Officer for the PDi, said, "After two very successful rounds of project selections, we are confident we can meet our industry partners' needs in terms of the quality and quantity of disease-relevant phenotypic assays. Since mid-2016 we have fine-tuned our operations, allowing us to build complex cell-based assays from innovative biology that we have crowdsourced from academic labs, clinicians, and subject matter experts. Our assay development teams have successfully developed this novel biology into screenable protocols that can be applied in multiparametric high content assays and carried out in high throughput formats."

The following five assays from PDi's second round of selections have been prioritised for development and compound library screening:

1. A High Content (HC) screen in human white blood cells will attempt to identify compounds that inhibit NLRP3 inflammasome activation. This assay, which focuses on one of the nodes of intracellular stress pathways, was submitted by Ana Andrezza's group at the Department of Pharmacology and Toxicology at the University of Toronto, and has immediate applications in bipolar disorder and other neuropsychiatric diseases."


2. Controlling neuroinflammation is also the focus of an assay put forward by John Davis from the Alzheimer's Research UK (ARUK) Oxford Drug Discovery Institute (ODDI), in this case applied to finding treatments for Alzheimer's disease. The phenotypic assay, based on a mouse bone marrow derived macrophages (BMDMs) cell line will be used as a model to find inhibitors of the NLRP3 inflammasome before further testing in human in vitro assays.

3. Stuart Forbes and Lara Campana at the MRC Centre for Regenerative Medicine, University of Edinburgh, provided PDi with a multiparametric flow cytometry-based assay that measures phagocytic performance in primary murine macrophages. Phagocytosis plays a key role in clearance of bacteria and apoptotic cells in infected or damaged tissues and its impairment has been implicated in chronic inflammatory diseases, autoimmune diseases and solid tumour oncology. NPSC will aim to find small molecules that stimulate mouse macrophage phagocytosis, whilst converting the model to utilise equivalent human cells.

4. Targeting immune suppressive molecules expressed by tumour-associated macrophages is thought to be a good way to improve efficacy of immunotherapy against metastatic breast cancer. NPSC will be working on a co-culture cell model in collaboration with Takanori Kitamura from the MRC Centre for Reproductive Health at the University of Edinburgh to find small molecules that inhibit macrophage-mediated Natural Killer (NK) cell suppression in order to enhance cell-based immunotherapies.

5. NPSC is working with Fiona Tulloch and Martin Ryan from the University of St. Andrews to establish a novel phenotypic screen aiming to discover small molecules to reduce the replication of enteroviruses that are increasing linked to mild and severe respiratory diseases. This novel safety-contained approach allows gene encoding viral capsid proteins to be replaced with a fluorescent reporter, allowing transcript RNA and genome replication to be monitored by live-cell imaging without the production of live pathogenic viruses. The long-term aim is to incorporate this assay methodology to the complex cellular model of the human bronchial epithelia that is in late-stage development within the NPSC in collaboration with Janssen Pharmaceutica NV.

The PDi assay portal remains open for project submissions: https://npsc.awardsplatform.com

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. Founding members are Janssen Pharmaceutica NV, part of the Pharmaceutical Companies of Johnson & Johnson, and the Universities of Dundee, Edinburgh and Oxford. PDi assays encompass the latest advances in primary, patient-derived and human induced Pluripotent Stem Cell (hiPSC) model systems combined with CRISPR/Cas9 gene editing, organoids and multicellular co-cultures. 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 screened against novel annotated and diverse chemical libraries, these assays generate pre-competitive data that is high-quality, physiologically relevant, and a potential start-point for drug development and aid the validation of new drug targets.
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
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
http://www.ed.ac.uk/biology

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Chancellor of the Exchequer visits NPSC

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Philip Hammond, Chancellor of the Exchequer, today visited the University of Dundee where he was given an insight into the world leading research being carried out in Life Sciences.

Dundee is the top-rated University in the UK for biological sciences research. Mr Hammond was given a tour of the School of Life Sciences including the Discovery Centre, the £50million building which was supported by direct funding from the UK Government.

The Chancellor visited  the National Phenotypic Screening Centre, where an interdisciplinary group of scientists and engineers are using innovative, high throughput imaging platforms that can be applied to human, animal, and plant health challenges.

Elements of the tour also included a visit to the Drug Discovery Unit, where work is ongoing to identify potential new treatments for some of the world’s major diseases. Scientists in the DDU developed the potential anti-malarial compound which is currently in advanced tests.

Life Sciences at Dundee has received more than £20 million in UK Government funding in recent years and is now ranked highly on global ratings for scientific excellence and impact of research.

The Chancellor, who also visited the site of the V&A Museum of Design Dundee (a project originated at the University), said:

'The work being done here at Dundee, with the support of the UK Government, is world leading and can have a transformative impact for people around the world, particularly those at risk from tropical diseases such as malaria.

'I have seen today how Dundee has benefitted from our life sciences and creative sector funding. I now look forward to progress being made on the Tay Cities Deal, which will follow the £1 billion already committed by the UK to Scotland’s City Deals so far.”

Professor Julian Blow, Dean of the School of Life Sciences at the University, said, “I was delighted to have the opportunity to show the Chancellor some of the work that has earned Dundee an international reputation as a centre of excellence in life sciences. We are committed to the highest quality teaching and research and ensuring that our work carries real impact. We do this with the help of staff and students who come to Dundee from around the world.”

NPSC Director is awarded Chemistry World Entrepreneur of the Year by RSC

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Professor Andrew Hopkins, NPSC's Director, is the 2017 Royal Society of Chemistry (RSC) - Chemistry World Entrepreneur of the year. This prestigious prize, is part of the 'Chemistry means business awards" and is awarded to individuals who demonstrated creativity and vision, driving chemistry innovation to commercial success for their business. Award winners are chosen by a panel of senior scientists and industry executives and selected for their contribution to innovation and commercial success. Andrew won the award for his role as CEO of the University of Dundee spin-out Exscientia, which he founded with co-worker and Exscientia-CTO Jérémy Besnard. Jérémy picked up the "Rising Star" award at the same ceremony. Exscientia, the first company to automate drug design, has also hit the headlines recently by signing two major multi-million strategic collaborations with GSK and Sanofi.

Read more about Andrew's career and aspirations in Chemistry World in Sarah Houlton's article: "Amplifying intelligent drug design".

Phenomics Discovery Initiative Announces First Phenotypic Assays Portfolio to Accelerate Translation of Novel Biology into Therapeutics

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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
http://www.ed.ac.uk/biology

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NPSC is part of the Phenomics Phenomenon

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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.

Link to Biocentury article by Michael Leviten

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