A new approach to Science at the Life Sciences Interface

Lead Research Organisation: University of Oxford
Department Name: Computer Science

Abstract

The key scientific challenges of the next century require that we fundamentally advance current understanding of complex natural systems - ranging from how cells work and why/how they go wrong, to how the interaction of climate and ecosystems regulates the planet's life support system. We wish to understand how these systems behave at the functional level, and how this behaviour arises as a result of highly dynamic, strongly non-linear, tightly coupled interactions between component processes occurring across multiple spatial and temporal scales. Entirely new kinds of exploratory and predictive models and research strategies are needed to address these challenges. A new generation of theoretical methods and tools are needed to enable the recognition and exploitation of synergies and similarities that allow the translation of solutions between different scientific problem domains. Biological theories are evaluated against often imperfect data sets. There is a need for judicious selection and validation of the test bed against which any model is evaluated and the development of novel technologies for gathering new data identified as critical to complex system behaviour. The investigation of systems-level behaviour requires the identification of biological hypotheses that could not have been expressed by looking at individual phenomena alone. The unprecedented degree of complexity will mean that these quantitative models will be analytically intractable, and exploring their behaviour will be possible only through a computational approach. In short, a novel computational approach and environment is needed for doing this kind of science - and this does not exist in academia today. Progress requires both a cultural and technological change in the way in which mathematical and computational models, tools and software are developed, and a concomitant change in the way in which groups of scientists are trained to develop and use these approaches. This work can only be done in the context of real biological problems. This proposal brings together a consortium of partners from academia and industry, each of whom has begun to focus on differing but complementary aspects of these problems. These centres are the ideal community to attempt such a cultural shift since they are already dedicated to training the next generation of scientists who will pioneer this kind of science.

Planned Impact

This proposal aims to train a new generation of first-rate scientists to lead, work and think across the boundaries of traditional scientific disciplines. At least 17 postdoctoral researchers will be trained directly by this proposal; they will work between disciplines and institutions as well as across academia and industry. The impact of this training will broaden over the lifetime of the grant as the PhD and DPhil students of the three DTCs (over 200 students during the lifetime of the grant) will be part of the community effort and be exposed to this multi-disciplinary, multi-site science. We will also train other members of the academic and industrial communities on the use of the in silico environment. The outputs of the programme - the in silico environment itself and the tools and techniques therein - will have an impact on the speed of scientific advances and the approaches used in the life sciences. Enabling the wider academic community to use the outputs of our work is vital to the success of the project. The computational modelling approaches we will develop will allow the analysis of complete system behaviour, targeting experimental power to areas with greatest potential impact. The computational models themselves must be robust and reusable, and we will develop an in silico infrastructure to facilitate this, thereby reducing the redundancy of disparate software environments. The integration of many existing tools and the development of new computational tools within this environment will allow significantly more life science researchers to carry out this type of research and increase the power of this type of analysis. Furthermore, some of society's current research challenges, such as understanding complex diseases or sustainable bioenergy, will only be solved by integrating biological and physical sciences research. As such, the outputs of this proposal will be of interest to both the academic and industrial sectors. Both of these communities will be engaged in our activities.

Publications

10 25 50

publication icon
Chapman NC (2017) The complexity of mating decisions in stalk-eyed flies. in Ecology and evolution

publication icon
Bruna M (2015) The effective flux through a thin-film composite membrane in EPL (Europhysics Letters)

publication icon
Todoric J (2013) Relationship of pentraxin 3 with insulin sensitivity in gestational diabetes. in European journal of clinical investigation

publication icon
Tazzyman SJ (2014) The handicap process favors exaggerated, rather than reduced, sexual ornaments. in Evolution; international journal of organic evolution

publication icon
Kuijper B (2014) Conflict over condition-dependent sex allocation can lead to mixed sex-determination systems. in Evolution; international journal of organic evolution

publication icon
Mullon C (2012) The effects of selection and genetic drift on the genomic distribution of sexually antagonistic alleles. in Evolution; international journal of organic evolution

publication icon
Tazzyman SJ (2014) Signaling efficacy drives the evolution of larger sexual ornaments by sexual selection. in Evolution; international journal of organic evolution

publication icon
Hadjivasiliou Z (2016) The evolution of mating type switching. in Evolution; international journal of organic evolution

publication icon
Kuijper B (2018) Maternal effects and parent-offspring conflict. in Evolution; international journal of organic evolution

publication icon
Johnston A (2013) The role of the harmonic vector average in motion integration. in Frontiers in computational neuroscience

publication icon
Cooper J (2014) Cellular cardiac electrophysiology modeling with Chaste and CellML. in Frontiers in physiology

publication icon
Pathmanathan P (2014) Verification of computational models of cardiac electro-physiology. in International journal for numerical methods in biomedical engineering

publication icon
Song Z (2015) Modelling the mechanoreceptor's dynamic behaviour. in Journal of anatomy

publication icon
Krawczyk K (2016) Tertiary Element Interaction in HIV-1 TAR. in Journal of chemical information and modeling

publication icon
Wilman HR (2014) Crowdsourcing yields a new standard for kinks in protein helices. in Journal of chemical information and modeling

 
Description Beyond the work described in the large number of research papers associated with this grant, the main findings to date relate to two key areas: the training and career development of the research fellows employed on the grant; and the methods employed for disseminating the research findings in a manner that makes the work both repeatable and reproducible.

In the first area, we have found that by making career and professional development a central of the programme, we have been able to achieve the remarkable success rate of obtaining either permanent academic posts or independent research fellowships detailed in the "Next Destination" section.

In the area of reproducible research, our approach is to develop on-line research communities where the outputs of computational science research can be shared in a manner that is designed to enable that research to be repeated and built upon. Examples of this approach are described in the Research Tools and Methods section (for example, the Zoon and Cardiac Weblab projects).
Exploitation Route We have already discussed our approach to career and professional development with key decision makers at EPSRC, BBSRC and the Wellcome Trust and hope to see some of our suggestions implemented as policy. We held a final project meeting which was attended by representatives of all of the RCUK funding bodies and the Welcome Trust to discuss lessons learnt and this was very well received and several follow-up meetings, enquiries and invitations have ensued.

The general approach to online communities is transferable to all areas of computational science.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology,Other

URL https://travis.cs.ox.ac.uk/FunctionalCuration/
 
Description We held a workshop on the Cardiac Electrophysiology Web Lab, which had 27 attendees from the cardiac modellng field, including from leading Pharma companies, senior figures and students. This was a 2 Day event hosted in Oxford. This has now lead to further funding (from BBSRC of £565K) supported by colleagues at the FDA in washington and at other leading research Universities worldwide. The BBSRC project has now started and we have submitted our first paper (which is under review).
First Year Of Impact 2015
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic,Policy & public services

 
Description Input into FDA Working Groups on Pro-arrhythmia
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Our approach to integrating information on multiple ion channel block is being suggested for uptake by pharmaceutical companies and regulators by an international working group for the CiPA initiative. Gary Mirams has attended a series of meetings and teleconferences to advise the CiPA Ion channel and In-silico modelling working groups.
URL http://www.ncbi.nlm.nih.gov/pubmed/24576511
 
Description AHRC Science in Culture Theme
Amount £79,432 (GBP)
Funding ID AH/N007085/1 
Organisation Arts & Humanities Research Council (AHRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 08/2017
 
Description AWS for Reproducible Computational Research
Amount $2,000 (USD)
Organisation Amazon.com 
Sector Private
Country United States
Start 05/2015 
End 06/2016
 
Description BBSRC responsive-mode grant
Amount £269,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start  
 
Description British Society for Immunology Travel Award (J Lewis)
Amount £1,000 (GBP)
Organisation British Society For Immunology 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2013 
End 01/2014
 
Description Doctoral Training
Amount £35,339 (GBP)
Funding ID NE/M006662/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 04/2014 
End 10/2014
 
Description EPSRC Impact Acceleration Account Award - Geoff Williams
Amount £60,211 (GBP)
Funding ID EP/K503769/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2014 
End 04/2015
 
Description EPSRC Impact Acceleration Account Award - Kylie Beattie
Amount £28,263 (GBP)
Funding ID EP/K503769/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2015 
End 08/2015
 
Description EPSRC Physics of Life Network "From Molecules to Systems" Collaboration Fund
Amount £5,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start  
 
Description Knowledge Exchange Seed Fund
Amount £2,000 (GBP)
Organisation University of Oxford 
Sector Academic/University
Country United Kingdom
Start 11/2013 
End 03/2014
 
Description Moffitt Cancer Center Pilot Grant
Amount $50,000 (USD)
Organisation Moffitt Cancer Centre 
Sector Academic/University
Country United States
Start  
 
Description Prediction of human cardiotoxic QT prolongation using in vitro multiple ion channel data and mathematical models of cardiac myocytes
Amount £176,136 (GBP)
Funding ID NC/K001337/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2013 
End 04/2014
 
Description Regulation through tissue size through patterned apoptosis
Amount £12,000 (GBP)
Funding ID IE130149 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2013 
End 06/2015
 
Description Reproducible development of mathematical models of cardiac electrophysiology
Amount £565,914 (GBP)
Funding ID BB/P010008/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 05/2017 
End 05/2020
 
Description Research Fellowship
Amount £39,000 (GBP)
Funding ID RF-2013-037 
Organisation The Leverhulme Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2013 
End 04/2015
 
Description Royal Society International Exchange Scheme
Amount £12,000 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Sir Henry Dale Fellowship
Amount £534,961 (GBP)
Funding ID 101222/Z/13/Z 
Organisation Sir Henry Dale Fellowships 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2014 
End 02/2019
 
Description Software Sustainability Fellowship (D Groen)
Amount £3,000 (GBP)
Organisation University of Edinburgh 
Department UK Software Sustainability Institute
Sector Academic/University
Country United Kingdom
Start 01/2014 
End 03/2015
 
Description Tansley Working Group: Information Visualisation for Science and Policy
Amount £26,000 (GBP)
Organisation Imperial College London 
Sector Academic/University
Country United Kingdom
Start  
 
Description University of Oxford IT Innovation Seed Fund
Amount £24,169 (GBP)
Organisation University of Oxford 
Sector Academic/University
Country United Kingdom
Start 08/2015 
End 07/2016
 
Title Action Potential Prediction Software 
Description We have released open source action potential prediction software https://chaste.cs.ox.ac.uk/trac/wiki/ApPredict that will allow anyone around the world to perform the simulations we have developed during the strategic award. The primary audience is pharmaceutical companies' Safety Pharmacology teams, who can enter data from ion channel screening experiments, and get a prediction of the whole-cell or whole-organ effect. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2014 
Provided To Others? Yes  
Impact This software is used in the web portal we have developed, detailed in the software section. 2017 - this tool has registered users with email addresses from 18 of the top 20 global pharmaceutical companies. 
URL https://chaste.cs.ox.ac.uk/ActionPotential/
 
Title Bacterial motility analysis tool (G Rosser and A Fletcher) 
Description Tracking bacteria using video microscopy is a powerful experimental approach to probe their motile behaviour. The trajectories obtained contain much information relating to the complex patterns of bacterial motility. However, methods for the quantitative analysis of such data are limited. Most swimming bacteria move in approximately straight lines, interspersed with random reorientation phases. It is therefore necessary to segment observed tracks into swimming and reorientation phases to extract useful statistics. Our research tool is a novel, robust analysis tool for discerning these two phases in tracks. Our tool comprises a simple and effective protocol for removing spurious tracks from tracking datasets, followed by analysis based on a two-state hidden Markov model, taking advantage of the availability of mutant strains that exhibit swimming-only or reorientating-only motion to generate an empirical prior distribution. This method has been shown to be substantially more robust to noise and introduce less systematic bias than existing heuristic analysis methods. 
Type Of Material Improvements to research infrastructure 
Year Produced 2013 
Provided To Others? Yes  
Impact Resulted in 3 publications, with DOIs 10.1098/rsif.2013.0273, 10.1371/journal.pcbi.1003276, 10.1098/rsif.2014.0320 
URL http://www.2020science.net/software/bacterial-motility-analysis-tool
 
Title Bayesian Inference of Parameters for Phototransduction Processes (Z Song) 
Description We have been developing a Bayesian Inference Framework to infer the 4 key parameters of phototransduction. Recent understandings imply that biological photoreceptors reply on 4 stochastic biophysical parameters to encode light stimuli into its neuronal response. To obtain a full picture of how these phototransduction work across the animal kingdom , it is preferably to measure these parameters in different animals and do comparison studies. However, experimental estimates of these parameters are either not available, or are expensive to obtain. Here, we provide a computational framework to do that. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact The project will result in a new tool that vision researchers can use to obtain a full picture of the underlying phototransduction process, in particular the role of the refractory period in visual signal encoding, which still remains somewhat mysterious because of our inability to directly measure this parameter experimentally. Furthermore, the framework would help save resources by also providing Bayesian estimates of the other parameters, which are currently obtained using many more costly experiments. The stochastic models we are analysing are very challenging to perform inference over, due to their computational complexity and the lack of analytic solutions, and they will motivate further advances in statistical methodology as we progress with this work. 
 
Title FabSim (D Groen and J Hetherington) 
Description FabSim is a Python-based automation toolkit for scientific simulation and data processing workflows. It aims to enable users to perform remote tasks from a local command-line, and to run applications while curating the environment variables and the input and output data in a systematic manner. To provide that curation, FabSim uses a basic data transfer functionalities such as rsync and ssh. 
Type Of Material Improvements to research infrastructure 
Year Produced 2014 
Provided To Others? Yes  
Impact Tbc 
URL https://github.com/djgroen/FabSim
 
Title Functional Curation 
Description Modellers have adopted XML-based markup languages to describe mathematical models over the past decade. This is great, as it means that models can be defined unambiguously, and shared easily, in a machine-readable format. We have been trying to do the same thing with 'protocols' - to define what you have to do to replicate/simulate an experiment, and analyse the results. We can then curate models according to their functional behaviour under a range of experimental scenarios. For the first time, we can thus easily compare how different models react to the same protocol, or compare how a model behaves under different protocols. 
Type Of Material Improvements to research infrastructure 
Year Produced 2014 
Provided To Others? Yes  
Impact Several papers have been written on the tool itself and its use within drug block studies. In addition it has highlighted errors in published CellML models (see http://mirams.wordpress.com/2013/10/22/importance-of-curating-models/). We have just received a BBSRC grant for £565K to extend this work. 
URL https://chaste.cs.ox.ac.uk/FunctionalCuration
 
Title MOSAICS 
Description Methods for Optimization and SAmpling In Computational Structural-biology (MOSAICS) is a sampling program developed to improve sampling efficiency by incorporating natural move-sets for proteins and nucleic acids 
Type Of Material Biological samples 
Year Produced 2007 
Provided To Others? Yes  
Impact MOSAICS provides applied scientists easy access to numerical methods in applied mathematics/statistics. Examples include but not limited to new Monte Carlo algorithms that brought all-atom mesoscale modelling within reach for the biophysics and computational biology communities. The use of NMMC expanded the boundaries of computational structural biology with key applications such as aiding the design of RNA nanotechnology, increasing the resolution of macromolecular Cryo-electron microscopy, atomistic prediction of primary chromatin structure and the epigenetic effect, modelling diabodies that tune extracellular receptor signaling to counteract intracellular oncogenic mutations, deciphering important molecular processes of the adaptive immune response. This software has been developed over the last ten years by Peter Minary. The fellow funded on this grant (Konrad Krwaczyk) has been working with Peter to develop user-friendly interfaces and applications for this software in the structural biology domain. 
URL http://www.cs.ox.ac.uk/mosaics
 
Title Model reduction for slow-fast stochastic systems with bistability (M Bruna) 
Description The method aims to reduce the complexity of modelling bistable systems which involve the interaction of two evolving species where one changes much faster than the other ("slow-fast systems"). In standard slow-fast systems, one usually tries to "average out" the fast variables resulting in a reduced model in the slow timescale. However, when the fast variables are bistable and the slow processes depend on them, it is not possible to use the standard techniques. Here we extended them to make this possible, and obtain a reduced model for the slow variable but which still captures accurately the impact of the bistable fast variable on the slow one. Starting from a stochastic slow-fast model where the fast variable is bistable, the method systematically obtains a reduced model at the slow timescale. This allows for easier computational simulations and predictions involving such systems, which are found in fields as diverse as chemistry, biology and ecology. 
Type Of Material Biological samples 
Year Produced 2013 
Provided To Others? Yes  
Impact The research paper we wrote on this method was published in the Journal of Chemical Physics 2014, and it was selected by the American Institute of Physics (AIP) to appear in a general public press release. As a result of the press release, which explains in lay terms some of the features of the method, we were contacted by researchers from the US "National Council Science and Environment" about possible applications of the method to tuna/human consumption, and the impact of catch quotas to the fish population. 
URL http://www.aip.org/publishing/journal-highlights/predator-prey-made-simple
 
Title ZO?N 
Description ZO?N aims to create a framework and online repository for Species Distribution Modelling that enables research to be more accessible, modifiable, extensible, repeatable, reproducible, reusable, shareable within the R statistical computing environment. 
Type Of Material Improvements to research infrastructure 
Year Produced 2014 
Provided To Others? Yes  
Impact Early stages of development, but convened an expert user panel to help test, revise and extend the ZO?N framework and interface. Student workshop planned for 2015. ZOON is now released on github and the first paper describing its development has just been submitted. 
URL http://zoonproject.wordpress.com/
 
Description Apoptosis-mediated pattern repair through EGFR signalling (A Fletcher) 
Organisation University of Notre Dame
Country United States 
Sector Academic/University 
PI Contribution Development of computational models and image analysis software for the study of apoptosis-mediated pattern repair through EGFR signalling (Dr. Alex Fletcher, with my colleague Dr Ruth Baker and my D.Phil. student Jochen Kursawe).
Collaborator Contribution The generation of live imaging and immunohistochemistry data for model parameterization and validation.
Impact Grant secured: Two-year Royal Society International Exchange Scheme funding (2013-2015; £12k). "Regulation of tissue size through patterned apoptosis". Main applicant: A. Fletcher. Co-applicant: J. Zartman. Grants submitted: £172,000 - A Fletcher named Senior Personnel on subcontract for NSF IOS proposal (submitted Jul 2014).; Apoptosis-mediated pattern repair through EGFR signaling. Co-authors: J. Zartman, R. Baker. £302,297 - NSF / UK BBSRC lead agency pilot opportunity scheme proposal (submitted Sep 2014). Exploring the role of calcium signalling in cell-cell competition. Principal Investigator: R. Baker. Project Partner: J. Zartman. This is a multi-disciplinary collaboration involving mathematical modelling, image analysis, chemical engineering, developmental biology.
Start Year 2012
 
Description Bayesian inference of neuronal data in the eye (Song and Calderhead) 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Contribution is the 4 parameter model recently developed and the recent understanding of phototransduction process.
Collaborator Contribution Dr. Ben Calderhead is developing new bayesian inference methods for better inference of stochastic models.
Impact A new Bayesian inference framework for phototranscution process has been developed. This collaboration will be multi-disciplinary. After we publish the framework in due course, we would like to further collaborate with electrophysiologists for inference on experimental data from real biological photoreceptors.
Start Year 2013
 
Description Biophysical modelling of mechanoreceptor neurons (Z Song) 
Organisation Durham University
Country United Kingdom 
Sector Academic/University 
PI Contribution Contribution is a new stochastic biophysical model for modelling mechanoreceptor neuronal response
Collaborator Contribution Dr. Guy Beswick will be collecting electrophysiology data for the project. Dr. Robert W. Banks will be supervising on the scientific questions.
Impact A new stochastic biophysical model for mechanosensory neuron has been developed. The project is multi-disciplinary. The experimental collaborators are anatomist or eletrophysioloigist from biological science or medical science department. A talk about the work was given at a symposium in University of Durham in September 2014, and the talk was received well so currently writing a paper for the modelling framework.
Start Year 2014
 
Description Biophysical modelling of mechanoreceptor neurons (Z Song) 
Organisation University of Aberdeen
Country United Kingdom 
Sector Academic/University 
PI Contribution Contribution is a new stochastic biophysical model for modelling mechanoreceptor neuronal response
Collaborator Contribution Dr. Guy Beswick will be collecting electrophysiology data for the project. Dr. Robert W. Banks will be supervising on the scientific questions.
Impact A new stochastic biophysical model for mechanosensory neuron has been developed. The project is multi-disciplinary. The experimental collaborators are anatomist or eletrophysioloigist from biological science or medical science department. A talk about the work was given at a symposium in University of Durham in September 2014, and the talk was received well so currently writing a paper for the modelling framework.
Start Year 2014
 
Description CD4 dynamics in HIV-infected infants delaying or interrupting ART (J Lewis) 
Organisation National Institute of Allergy and Infectious Diseases (NIAID)
Department Children with HIV Early Antiretroviral Study (CHER)
Country United States 
Sector Public 
PI Contribution Mathematical and statistical modelling and analysis
Collaborator Contribution Supplied data collected during a clinical trial
Impact No outcomes as yet. The collaboration is multidisciplinary, involving clinical (trial management; study design), mathematical/statistical (modelling data analysis) and biological (interpretation of results) input.
Start Year 2013
 
Description Chemical & Biomolecular Engineering 
Organisation University of Notre Dame
Country United States 
Sector Academic/University 
PI Contribution Alexander Fletcher was working with Jeremy Zartman (Assistant Professor), at the University of Notre Dame on several projects in the area of tissue size control in embryonic epthelia. Alexander and Jeremy have co-authored two papers to date, with another three in preparation. Alexander is a named collaborator with Jeremy on a NIH proposal under review, which if successful will fund a 3 year PDRA position at Sheffield University to implement 3d vertex models of epithelial tissue size control
Collaborator Contribution N/a
Impact Co-authored two papers
Start Year 2015
 
Description Collaboration between Antoine Coutrot and Dr Olivier Le Meur 
Organisation University of Rennes 1
Country France 
Sector Academic/University 
PI Contribution Antoine Coutrot worked with Dr Le Meur to propse a new model of visual attention.
Collaborator Contribution Dr Le Meur's databases and model were used to propose a new model of visual attention
Impact We published a paper 10.1016/j.visres.2016.01.005 and a conference proceedings: Le Meur O, Antoine Coutrot. How saccadic models help predict where we look during a visual task? Application to visual quality assessment. IST International Symposium on Electronic Imaging Image Quality and System Performance XIII, San Francisco, USA: 2016.
Start Year 2014
 
Description Institute for Food Research 
Organisation Quadram Institute Bioscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Alexander Fletcher is part of a BBSRC grant which funds two PDRAs to study crypt-villus homeostasis and regenration in the intestinal epithelium.
Collaborator Contribution To be added
Impact To be added
Start Year 2015
 
Description Myosin II polarization during convergence-extension 
Organisation University of Cambridge
Department Department of Physiology, Development and Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Alexander Fletcher is working with the University of Cambridge and currently have a manuscript under review at eLife based on this work, as well as a BBSRC TRDF2 proposal under review that if successful would fund a 1 year PDRA shared between Sheffield and Cambridge to build on modelling work to date.
Collaborator Contribution To be added
Impact No impact yet
Start Year 2015
 
Description Roche Safety Pharmacology Collaboration 
Organisation F. Hoffmann-La Roche AG
Department Safety Pharmacology
Country United Kingdom 
Sector Private 
PI Contribution We have instigated a collaboration and have helped to write an internal Roche case for support to get funding to work together. Gary Mirams, Ken Wang and Geoff Williams visited Safety Pharmacology, Basel to give a talk and discuss collaborations in July 2014.
Collaborator Contribution The partners visited Oxford in November 2013. They have supported an internal grant which has resulted in Gary Mirams being appointed as an Academic Mentor for Ken Wang (and will involve some funds being transferred to Oxford). Roche has also helped to define a PhD project for Ross Johnstone.
Impact A 2 year industrial postdoctoral fellowship will be starting in January 2015 for Ken Wang, a PhD student who works with Gary Mirams (PI) and David Gavaghan (Co-I). Further to this, we now have a joint Industrial Doctoral Training Centre student Ross Johnstone who has started a PhD with Remi Bardenet, David Gavaghan and Gary Mirams at Oxford, and Liudmila Polonchuk and Mark Davies at Roche.
Start Year 2013
 
Description Tooth placode morphogenesis in the mouse 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Alexander Fletcher's contribution is the development of an immersed boundary model of epithelial bounding. Co-supervision of a third year student at the University of Oxford. Also a HFSP application woth Professor Jeremy Green and Dr Ophir Klein (UCSF)
Collaborator Contribution To be added
Impact To be added
Start Year 2015
 
Title ApPredict 
Description Cardiac safety simulation C++ software project built on top of 'Chaste'. This software was written by Dr Gary Mirams to perform cardiac electrophysiology simulations for safety pharmacology teams. Latest release to go with Chaste 2017.1 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Used in ApPredict Online web portal. 
URL https://chaste.cs.ox.ac.uk/trac/wiki/ApPredict
 
Title ApPredict Online 
Description This is an open source web portal front end to the ApPredict simulation software. It allows users to enter data on drug-induced blockade of different ion channels, to run simulations with ApPredict, and to store and plot the results in the web browser. 
Type Of Technology Webtool/Application 
Year Produced 2018 
Open Source License? Yes  
Impact Over 10 of the top 20 largest global pharmaceutical companies have now registered for accounts on the Web Portal. The portal is used in-house at both GlaxoSmithKline and HoffmanLa-Roche by their safety pharmacology teams. 
URL https://chaste.cs.ox.ac.uk/ActionPotential/
 
Title Chaste 
Description Chaste - Cancer, Heart and Soft Tissue Environment is a C++ library for computational biology. It was first released open source in 2009. Release 3.2 happened in 2014 
Type Of Technology Software 
Year Produced 2014 
Open Source License? Yes  
Impact Many international groups have made use of our software for a wide variety of applications, details on the website and twitter feed: https://twitter.com/Chaste_Project 
URL http://www.cs.ox.ac.uk/chaste
 
Title MOSAICS 
Description Methods for Optimization and SAmpling In Computational Structural-biology (MOSAICS) is a sampling program developed to improve sampling efficiency by incorporating natural move-sets for proteins and nucleic acids. 
Type Of Technology Software 
Year Produced 2015 
Open Source License? Yes  
Impact MOSAICS provides applied scientists easy access to numerical methods in applied mathematics/statistics. Examples include but not limited to new Monte Carlo algorithms that brought all-atom mesoscale modelling within reach for the biophysics and computational biology communities. The use of NMMC expanded the boundaries of computational structural biology with key applications such as aiding the design of RNA nanotechnology, increasing the resolution of macromolecular Cryo-electron microscopy, atomistic prediction of primary chromatin structure and the epigenetic effect, modelling diabodies that tune extracellular receptor signaling to counteract intracellular oncogenic mutations, deciphering important molecular processes of the adaptive immune response. This software has been developed over the last ten years by Peter Minary. The fellow funded on this grant (Konrad Krwaczyk) has been working with Peter to develop user-friendly interfaces and applications for this software in the structural biology domain. 
URL http://www.cs.ox.ac.uk/mosaics
 
Title ZO?N 
Description ZO?N aims to create a framework and online repository for Species Distribution Modelling that enables research to be more accessible, modifiable, extensible, repeatable, reproducible, reusable, shareable within the R statistical computing environment. 
Type Of Technology Software 
Year Produced 2014 
Impact Convened an expert user panel to help test, revise and extend the ZO?N framework and interface. 
URL https://zoonproject.wordpress.com/
 
Description Communication Advisor, Biodiversity and Ecosystem Service Sustainability (BESS) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Advise on the most effective means of communicating BESS science to the user community, from management to policy. Awarding Body - Biodiversity and Ecosystem Service Sustainability, NERC.

Ongoing, TBC
Year(s) Of Engagement Activity 2013,2014
 
Description FDA / HESI / Cardiac Safety Research Consortium: Invited speaker 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact 200 pharmaceutical company and regulatory authority representatives attended a workshop where the "Comprehensive In-vitro Pro-arrhythmia Assay (CiPA)" was suggested. The aim is to replace a human clinical trial with a mixture of ion channel screening, stem-cell derived myocytes, and mathematical modelling.

I presented a talk on behalf of the computational modelling community at the FDA research facility in White Oak, Maryland, USA. I highlighted where computational models could be used in the FDA's switch to a new pre-clinical safety assessment, rather than the Thorough QT human clinical trial.
Year(s) Of Engagement Activity 2013
URL http://www.hesiglobal.org/i4a/pages/index.cfm?pageID=3620
 
Description Open Science Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Promoted ideas of Open Science via Royal Society launch of new journal.

Unknown, currently the interview has been viewed 125 times.
Year(s) Of Engagement Activity 2014
URL http://youtu.be/UF7crpzf850
 
Description Pint of Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Around 40 people attended a talk and questions by myself and Dr Rebecca Burton.

Well attended talk
Year(s) Of Engagement Activity 2013
URL http://www.pintofscience.com/#!oxford-body/c1bv8
 
Description School crowdsourcing project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact Involvement of 70 pupils of the Junior Highschool Rottenmann in a crowd sourcing project

Subsequent newspaper articles about the project in the "Stadtkurier", 2013-2014
Year(s) Of Engagement Activity 2013
 
Description Talk at British Science Festival 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact ~125 people attended a talk on 'Lifesaving Mathematics' by Thomas Wooley, Helen Byrne, and me.

Quite a few follow-up questions from an interested audience.
Year(s) Of Engagement Activity
URL http://www.britishscienceassociation.org/british-science-festival/life-saving-mathematics
 
Description Virtual body double gets ill so you don't have to 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact New Scientist article.

Increase in media requests.
Year(s) Of Engagement Activity 2013
URL http://www.newscientist.com/article/mg21729066.000-virtual-body-double-gets-ill-so-you-dont-have-to....