Bridging systems biology and advanced computing, to realise multi-scale biological modelling.

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The life sciences are in the midst of an unparalleled expansion, so much that the 21st-century has been termed "the century of biology". This interchange Fellowship will recruit the experience from a world-leading centre for computational science, EPCC, personified by Alastair Hume one of its senior software architects, to build a long-term partnership that maintains the U.K.'s advantage at the forefront of Biology. Such expertise is urgently required, because mathematical and computational modelling is the next driver of progress for a broad and growing swathe of life science research. The publication of a ground-breaking "whole-cell" model (Karr et al., 2012) has galvanised this research in the field of Systems Biology, by representing the function of every gene in a (very simple) cell. This landmark in multi-scale modelling bridges from the genome to cell function. Physiological models already exist that span from cellular to organ and organism level, not only in the pioneering mammalian heart model but also in the plant-level models of crop science. Thus the "whole-cell" model is a crucial step towards a link from genotype to phenotype or from genome sequence to clinical traits. The plant models link even further, to the field scale and to larger agricultural and ecological models that routinely contribute to crop and climate forecasting.The whole-cell model's authors are among many to stress that biologists must collaborate with computer scientists in data curation, model integration, accelerated computation and data analysis (Macklin et al.). Standards and software must constantly evolve to keep pace. Working, exemplar models are essential to specify the next-generation solutions. Researchers at SynthSys are using the "whole-cell" exemplar model and developing models for more complex cells. SynthSys was established by BBSRC and EPSRC as one of six UK Systems Biology centres, to focus on modelling cell and molecular biology. Andrew Millar's group has developed a whole-plant Framework Model of Arabidopsis growth, building on this major BBSRC investment. It is not only one of the very few exemplars that can be used to specify future computational infrastructure, but is also supporting a growing link from fundamental Systems Biology to Crop Science.We are privileged to work with Alastair Hume, who ideally meets the urgent needs of our current research. Hume has over 20 years' experience in software development in industry and academia. While working at EPCC over the last 14 years, he has led the design and implementation of scalable data integration, processing and analysis systems for a variety of research fields ranging from astronomy to environmental modelling and prediction. In the recent EU BonFIRE project, for example, he led a team of up to 20 software developers working on future cloud computing.Hume has already demonstrated his potential in joint, pilot projects with SynthSys and he is now poised to make a long-term contribution. The Fellowship is essential to realise that interdisciplinary conversion, allowing him to train in systems biology including an internship at the EBI, to engage with the broader systems biology modelling community, as well as addressing demonstration projects in three areas. Our multiscale models explicitly aim to link researchers from different scientific backgrounds, who must work together to provide the data, the modelling components and validation experiments. The Fellowship will provide time for this crucial networking, in the UK and USA, and with our partners at Rothamsted Research and Simulistics Ltd. This Fellowship will allow SynthSys and EPCC jointly to link our work to international leaders in both computational resources and in biological modelling, creating a commanding position for the U.K.'s research and Alastair Hume in particular, at the nexus of three fast-moving areas: plant systems biology, cyber-infrastructure and multi-scale crop modelling.