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News Article | May 22, 2017
Site: phys.org

Xenopus are aquatic frogs native to sub-Saharan Africa and one of the mainstays of science in understanding disease and healthy development in humans. The frogs became popular in science because from the 1940s to the 1960s they were used worldwide as a pregnancy test. Doctors would ship women's urine samples to frog laboratories, a sample would be injected into the hind leg of a frog, and if, the next morning, the frog had laid eggs, doctors were 100 per cent confident a woman was pregnant. Research by the University's Institute of Biomedical and Biomolecular Science has shown it's possible – and, crucially, simple – to make 32 embryos from one sample of sperm, instead of the current 4-8. By freezing sperm rather than using it fresh, thousands of male frogs will now not need to be humanely killed and the welfare of those used will be improved. Professor of Developmental Genetics at the university Matt Guille led the study, published in the journal Theriogenology. He said: "We've made the process very simple so it can be replicated easily, and it's very effective. Critically, it also greatly enhances animal welfare – hormone levels show frogs are stressed when sent via airfreight around the world, now it seems highly likely that male Xenopus won't have to be. "It will be a big saving internationally in the number of male frogs used in research." The University of Portsmouth houses the European Xenopus Resource Centre, the world's largest Xenopus research facility, and which makes, houses and distributes genetically altered clawed frogs, frog sperm and frog embryos to more than 150 medical research laboratories worldwide. The research team is now refining the process further and testing it by sending samples to laboratories in Japan, the US and in Europe in a project funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Once feedback has been received and any tweaks made to the method, it will be rolled out across the other Xenopus resource centres in the US and Japan. The advances it has now made are likely to help laboratories worldwide also reduce the number of frogs they use for research. Explore further: Why frogs need saving More information: Esther Pearl et al. An optimized method for cryogenic storage of Xenopus sperm to maximise the effectiveness of research using genetically altered frogs, Theriogenology (2017). DOI: 10.1016/j.theriogenology.2017.01.007


The company has been developing comprehensive platforms of computer-generated models for protein structures in the human body. Using the latest high-performance computing technology, they are now able to run millions of mathematical simulations over short spaces of time to determine how all these proteins interact with various chemical compounds they are exposed to in real-life conditions. This means the company can rapidly accelerate discovery of new drug leads as well as predict whether a compound will provoke an Adverse Drug Reaction (ADR) in the human body. The high cost of drug development is a major obstacle to finding cures for many diseases. Although the exact figures are disputed, some experts put the cost of drug development today at £1.15bn per drug. Over half the resources needed to develop a new drug are required at the various clinical trial stages. Moleculomics was set up by Dr Jonathan Mullins at Swansea University's Medical School, and was supported by the University's Research, Engagement and Innovation Services team. The company funds 2 senior researchers and 4 PhD students at the University. Moleculomics are now in the process of developing a new set of tools and processes which will allow us to distinguish between a "safe" drug destined for market and a "bad" drug destined to be withdrawn from the development process due to toxic effects towards the beginning of the drug development process. They will also shortly be launching their flagship product Human3DProteome. This will, for the first time, enable the high throughput screening of candidate small molecule compounds against every protein in the human body - a library of 30,000+ potential drug targets. The programme of research receives funding from the Government of Canada, the UK Ministry of Defence, Unilever, Dow and NC3Rs. Dr Jonathan Mullins, founder and CEO of the Moleculomics group, and an academic at Swansea University, said: "It's an exciting development that addresses head-on why certain compounds make good, generally safe, drugs and others are associated with more toxicity to the human body, by profiling the intricate interactions that they have with many hundreds of receptors" Dr Will Krawszik, Head of Operations for Moleculomics, and a former member of staff at Swansea University, said: "This will provide a tool which can predict the outcome of a drug development project before even entering the laboratory, all using the latest supercomputing technology and some highly innovative algorithms" The workflows being developed as part of this solution will provide: By conducting computer based in silico analysis at the beginning of the drug discovery stage, many more potential drugs can be considered for a greater diversity of therapeutic applications. Drugs that are likely to fail would be taken out of the process before clinical trials begin, allowing more resources to be placed on those that are likely to succeed. Given over half the resources taken to develop a new drug are required at the various Clinical Trial stages, the time and cost saving of this new technology is huge, and the impact on the global population, potentially profound. Explore further: Study says drugs could be developed cheaper and faster


News Article | May 4, 2017
Site: www.eurekalert.org

Getting better drugs to market faster, and at a fraction of the cost, is a step closer thanks to technology for speeding up the testing process, which is being developed by a Swansea University spin-out company, Moleculomics. The company has been developing comprehensive platforms of computer-generated models for protein structures in the human body. Using the latest high-performance computing technology, they are now able to run millions of mathematical simulations over short spaces of time to determine how all these proteins interact with various chemical compounds they are exposed to in real-life conditions. This means the company can rapidly accelerate discovery of new drug leads as well as predict whether a compound will provoke an Adverse Drug Reaction (ADR) in the human body. The high cost of drug development is a major obstacle to finding cures for many diseases. Although the exact figures are disputed, some experts put the cost of drug development today at £1.15bn per drug. Over half the resources needed to develop a new drug are required at the various clinical trial stages. Moleculomics was set up by Dr Jonathan Mullins at Swansea University's Medical School, and was supported by the University's Research, Engagement and Innovation Services team. The company funds 2 senior researchers and 4 PhD students at the University. Moleculomics are now in the process of developing a new set of tools and processes which will allow us to distinguish between a "safe" drug destined for market and a "bad" drug destined to be withdrawn from the development process due to toxic effects towards the beginning of the drug development process. They will also shortly be launching their flagship product Human3DProteome. This will, for the first time, enable the high throughput screening of candidate small molecule compounds against every protein in the human body - a library of 30,000+ potential drug targets. The programme of research receives funding from the Government of Canada, the UK Ministry of Defence, Unilever, Dow and NC3Rs. Dr Jonathan Mullins, founder and CEO of the Moleculomics group, and an academic at Swansea University, said: "It's an exciting development that addresses head-on why certain compounds make good, generally safe, drugs and others are associated with more toxicity to the human body, by profiling the intricate interactions that they have with many hundreds of receptors" Dr Will Krawszik, Head of Operations for Moleculomics, and a former member of staff at Swansea University, said: "This will provide a tool which can predict the outcome of a drug development project before even entering the laboratory, all using the latest supercomputing technology and some highly innovative algorithms" The workflows being developed as part of this solution will provide: a powerful open-ended, lead discovery environment, identifying on-target and off-target interactions across the whole proteome; detailed characterisation of active sites and millions of protein-compound interactions, involving thousands of lead compounds, screened for interaction with 1,500 drug targets of known pharmacological and therapeutic action; a drug repurposing platform featuring all 1,600 FDA approved drugs and tens of thousands of new repurposing leads. By conducting computer based in silico analysis at the beginning of the drug discovery stage, many more potential drugs can be considered for a greater diversity of therapeutic applications. Drugs that are likely to fail would be taken out of the process before clinical trials begin, allowing more resources to be placed on those that are likely to succeed. Given over half the resources taken to develop a new drug are required at the various Clinical Trial stages, the time and cost saving of this new technology is huge, and the impact on the global population, potentially profound. About Moleculomics: as a vehicle for the advancement of alternative technologies for small molecule discovery and purposing, Moleculomics, a UK university spin-out company formed in 2012, has developed powerful in silico protein structural modelling and ligand docking platforms, at proteome-scale, for simulating real-life conditions and molecular interactions at whole system level. R&D is built on a track record of structural modelling research featured in more than 50 journal publications. Over the past four years Moleculomics have been delivering commercial R&D programs including both Hit-to-Lead and toxicity screening work in prestigious projects with UK Ministry of Defence (MoD), Unilever, Dow and NC3Rs resulting in a range of technologies described as "world leading". For more information, please visit http://www. Swansea University is a world-class, research-led, dual campus university. The University was established in 1920 and was the first campus university in the UK. It currently offers around 350 undergraduate courses and 350 postgraduate courses to circa 20,000 undergraduate and postgraduate students. The University's 46-acre Singleton Park Campus is located in beautiful parkland with views across Swansea Bay. The University's 65-acre science and innovation Bay Campus, which opened in September 2015, is located a few miles away on the eastern approach to the city. It has the distinction of having direct access to a beach and its own seafront promenade. Both campuses are close to the Gower Peninsula, the UK's first Area of Outstanding Natural Beauty. Swansea is ranked the top university in Wales and is currently The Times and The Sunday Times 'Welsh University of the Year'. It is also ranked within the top 350 best universities in the world in the Times Higher Education World University rankings. The results of the Research Excellence Framework (REF) 2014 showed the University has achieved its ambition to be a top 30 research University, soaring up the league table to 26th in the UK, with the 'biggest leap among research-intensive institutions' (Times Higher Education, December 2014) in the UK. The University has ambitious expansion plans as it moves towards its centenary in 2020, as it continues to extend its global reach and realising its domestic and international ambitions. Follow us on Twitter: http://www. Find us on Facebook: http://www.


PubMed | GSK., Health Canada., U.S. FDA., ASCR. and 7 more.
Type: | Journal: Pharmeuropa bio & scientific notes | Year: 2016

The International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: Progress and Challenges in the Replacement of HIST was held on 24 August 2014, in Prague, Czech Republic, as a satellite meeting to the 9th World Congress on Alternatives and Animal Use in the Life Sciences. Participants discussed the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine sensitisation test (HIST) for acellular pertussis vaccines. Discussions focused on the consistency approach, the necessary framework for regulatory acceptance of a harmonised method, and recent international efforts towards the development of in vitro assays to replace the HIST. Workshop participants agreed that acceptable alternatives to the HIST should be based on ADP ribosylation-mediated cell intoxication and therefore that the CHO cell clustering assay, which measures cell intoxication, should be further pursued and developed as a possible replacement for the HIST. Participants also agreed to continue ongoing multinational discussions involving national and international standardisation authorities to reach consensus and to organise collaborative studies in this context for assay characterisation and calibration of reference materials.


PubMed | NC3Rs, BASF, Dow AgroSciences and Hill International
Type: | Journal: Regulatory toxicology and pharmacology : RTP | Year: 2016

The European Plant Protection Products Regulation 1107/2009 requires that registrants establish whether pesticide metabolites pose a risk to the environment. Fish acute toxicity assessments may be carried out to this end. Considering the total number of pesticide (re-) registrations, the number of metabolites can be considerable, and therefore this testing could use many vertebrates. EFSAs recent Guidance on tiered risk assessment for plant protection products for aquatic organisms in edge-of-field surface waters outlines opportunities to apply non-testing methods, such as Quantitative Structure Activity Relationship (QSAR) models. However, a scientific evidence base is necessary to support the use of QSARs in predicting acute fish toxicity of pesticide metabolites. Widespread application and subsequent regulatory acceptance of such an approach would reduce the numbers of animals used. The work presented here intends to provide this evidence base, by means of retrospective data analysis. Experimental fish LC50 values for 150 metabolites were extracted from the Pesticide Properties Database (http://sitem.herts.ac.uk/aeru/ppdb/en/atoz.htm). QSAR calculations were performed to predict fish acute toxicity values for these metabolites using the US EPAs ECOSAR software. The most conservative predicted LC50 values generated by ECOSAR were compared with experimental LC50 values. There was a significant correlation between predicted and experimental fish LC50 values (Spearman rs=0.6304, p<0.0001). For 62% of metabolites assessed, the QSAR predicted values are equal to or lower than their respective experimental values. Refined analysis, taking into account data quality and experimental variation considerations increases the proportion of sufficiently predictive estimates to 91%. For eight of the nine outliers, there are plausible explanation(s) for the disparity between measured and predicted LC50 values. Following detailed consideration of the robustness of this non-testing approach, it can be concluded there is a strong data driven rationale for the applicability of QSAR models in the metabolite assessment scheme recommended by EFSA. As such there is value in further refining this approach, to improve the method and enable its future incorporation into regulatory guidance and practice.


PubMed | Hill International, NC3Rs, University of Plymouth, Cefas Fisheries Laboratory and 5 more.
Type: Journal Article | Journal: Integrated environmental assessment and management | Year: 2016

The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing. The group recently held a workshop to identify the areas of testing, demands, and drivers that will have an impact on the future of animal use in regulatory ecotoxicology. As a result of these discussions, we have developed a pragmatic approach to prioritize and realistically address key opportunity areas, to enable progress toward the vision of a reduced reliance on the use of animals in this area of testing. This paper summarizes the findings of this exercise and proposes a pragmatic strategy toward our key long-term goals-the incorporation of reliable alternatives to whole-organism testing into regulations and guidance, and a culture shift toward reduced reliance on vertebrate toxicity testing in routine environmental safety assessment. Integr Environ Assess Manag 2016;12:417-421. 2015 SETAC.


Burden N.,NC3Rs | Mahony C.,Procter and Gamble | Muller B.P.,Symrise AG | Terry C.,Dow AgroSciences | And 2 more authors.
Toxicology | Year: 2015

There are currently several factors driving a move away from the reliance on in vivo toxicity testing for the purposes of chemical safety assessment. Progress has started to be made in the development and validation of non-animal methods. However, recent advances in the biosciences provide exciting opportunities to accelerate this process and to ensure that the alternative paradigms for hazard identification and risk assessment deliver lasting 3Rs benefits, whilst improving the quality and relevance of safety assessment. The NC3Rs, a UK-based scientific organisation which supports the development and application of novel 3Rs techniques and approaches, held a workshop recently which brought together over 20 international experts in the field of chemical safety assessment. The aim of this workshop was to review the current scientific, technical and regulatory landscapes, and to identify key opportunities towards reaching these goals. Here, we consider areas where further strategic investment will need to be focused if significant impact on 3Rs is to be matched with improved safety science, and why the timing is right for the field to work together towards an environment where we no longer rely on whole animal data for the accurate safety assessment of chemicals. © 2015 Z.


PubMed | NC3Rs, University of Plymouth, Dow AgroSciences and Organisation for Economic Co-operation and Development
Type: | Journal: Regulatory toxicology and pharmacology : RTP | Year: 2016

Fish toxicity testing has been conducted since the 1860s in order to help define safe levels of chemical contaminants in lakes, rivers and coastal waters. The historical emphasis on acute lethality testing of chemicals has more recently focussed on long term sublethal effects of chemicals on fish and their prey species. Fish toxicity testing is now embedded in much environment legislation on chemical safety while it is recognized that animal use should be Replaced, Reduced and Refined (the 3Rs) where possible. The OECD Fish Toxicity Testing Framework provides a useful structure with which to address the needs of environmental safety assessment whilst implementing the 3Rs. This commentary aims to promote the implementation of the recommendations of the OECD Fish Toxicity Testing Framework.


News Article | December 20, 2016
Site: www.eurekalert.org

Researchers have won a major new grant award for a study that will help to improve the welfare of live fish used in scientific tests. After rodents, fish are the second most commonly used animal in laboratory research and testing. However, the methods currently used for monitoring their welfare such as checking activity levels, stress hormones post mortem and clinical signs, are of limited value. These methods can often be ambiguous, invasive and provide feedback too late for researchers to act on. Scientists specialising in animal behaviour, cognition and welfare from the University of Lincoln, UK, have secured grant funding of more than £300,000 to devise an effective new tool for assessing the welfare of fish. Funded by the NC3Rs (National Centre for the Replacement Refinement & Reduction of Animals in Research), the project will develop and validate an automated 'social network' analysis tool using computer systems that will monitor changes in social interactions within groups of zebrafish and rainbow trout, and identify those changes which provide early warning signs of compromised welfare. The research will also examine how interventions designed to improve welfare, such as enriching the fishes' environment, impact on their behaviour. The three-year project will be led by Dr Oliver Burman, together with his co-investigator Dr Thomas Pike - both from the School of Life Sciences at the University of Lincoln. Dr Burman said: "Fish are increasingly popular as a research model, and we know that they can experience pain and demonstrate aversive behaviour when involved in scientific studies. There is therefore a clear and urgent need to identify ways in which we can refine the procedures used to assess fish welfare." The project will build up an extensive bank of knowledge and data about how groups of zebrafish and rainbow trout interact with each other in different conditions. Observations of the frequency, strength, type and direction of their associations with each other will be analysed to reveal to what extent deviations from their normal behaviour can inform us about their wellbeing. Dr Pike explained: "By developing a system that immediately recognises and alerts us to the first signs of distress, we hope to be able to ensure that fish welfare is protected whenever they are used in a scientific study." The funding was awarded as part of the NC3Rs 2016 project grant competition, which supports new approaches to reducing reliance on animals in research and improving animal welfare.

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