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

连接系统生物学和先进计算，实现多尺度生物建模。

• 批准号: BB/M017605/1
• 负责人: Andrew Millar
• 金额: $ 17.65万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM017605%2F1
• 关键词: Bridging; systems; biology; advanced; computing

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.

生命科学正处于前所未有的扩张之中，以至于21世纪被称为“生物学的世纪”。该交流奖学金将从世界领先的计算科学中心EPCC（由其高级软件架构师之一Alastair Hume代表）招募经验，以建立长期合作伙伴关系，维护英国。的优势在生物学的前沿。这种专业知识是迫切需要的，因为数学和计算建模是广泛和不断增长的生命科学研究的下一个进步动力。突破性的“全细胞”模型（Karr等人，2012）通过代表（非常简单的）细胞中每个基因的功能，激发了系统生物学领域的这项研究。这是多尺度建模的里程碑，将基因组与细胞功能联系起来。生理模型已经存在，从细胞到器官和生物体水平，不仅在开创性的哺乳动物心脏模型中，而且在作物科学的植物水平模型中。因此，“全细胞”模型是从基因型到表型或从基因组序列到临床特征的关键一步。植物模型的联系甚至更进一步，到田间规模和更大的农业和生态模型，通常有助于作物和气候预测。全细胞模型的作者和许多人强调，生物学家必须与计算机科学家合作，进行数据管理，模型集成，加速计算和数据分析（Macklin等人）。标准和软件必须不断发展以跟上步伐。有效的范例模型对于指定下一代解决方案至关重要。SynthSys的研究人员正在使用“全细胞”模型，并为更复杂的细胞开发模型。SynthSys由BBSRC和EPSRC建立，是英国六个系统生物学中心之一，专注于细胞和分子生物学建模。安德鲁米勒的小组已经开发了一个拟南芥生长的全植物框架模型，建立在BBSRC的这一重大投资的基础上。它不仅是可用于指定未来计算基础设施的极少数范例之一，而且还支持从基础系统生物学到作物科学的日益增长的联系。我们很荣幸与阿拉斯泰尔·休谟合作，他理想地满足了我们当前研究的迫切需求。Hume在工业和学术界拥有超过20年的软件开发经验。在过去的14年里，他在EPCC工作，领导了从天文学到环境建模和预测等各种研究领域的可扩展数据集成，处理和分析系统的设计和实施。例如，在最近的欧盟BonFIRE项目中，他领导了一个由20名软件开发人员组成的团队，致力于未来的云计算。Hume已经在与SynthSys的联合试点项目中展示了他的潜力，现在他准备做出长期贡献。奖学金是实现跨学科转换的关键，使他能够接受系统生物学培训，包括在EBI实习，与更广泛的系统生物学建模社区合作，以及解决三个领域的示范项目。我们的多尺度模型明确旨在将来自不同科学背景的研究人员联系起来，他们必须共同努力提供数据，建模组件和验证实验。该奖学金将为英国和美国的这一关键网络提供时间，并与我们在Rothamsted Research和Simulistics Ltd.的合作伙伴一起，该奖学金将使SynthSys和EPCC共同将我们的工作与计算资源和生物建模方面的国际领导者联系起来，为英国创造一个制高点。的研究，特别是阿拉斯泰尔·休谟，在三个快速发展的领域的联系：植物系统生物学，网络基础设施和多尺度作物建模。

项目成果

Crops In Silico: Generating Virtual Crops Using an Integrative and Multi-scale Modeling Platform.

• DOI: 10.3389/fpls.2017.00786
• 发表时间: 2017
• 期刊: Frontiers in plant science
• 影响因子: 5.6
• 作者: Marshall-Colon A;Long SP;Allen DK;Allen G;Beard DA;Benes B;von Caemmerer S;Christensen AJ;Cox DJ;Hart JC;Hirst PM;Kannan K;Katz DS;Lynch JP;Millar AJ;Panneerselvam B;Price ND;Prusinkiewicz P;Raila D;Shekar RG;Shrivastava S;Shukla D;Srinivasan V;Stitt M;Turk MJ;Voit EO;Wang Y;Yin X;Zhu XG
• 通讯作者: Zhu XG

A multi-model Framework for the Arabidopsis life cycle

拟南芥生命周期的多模型框架

• DOI: 10.1101/358408
• 发表时间: 2018
• 作者: Zardilis A

Plants in silico: why, why now and what?--an integrative platform for plant systems biology research.

• DOI: 10.1111/pce.12673
• 发表时间: 2016-05
• 期刊: Plant, cell & environment
• 作者: Xinguang Zhu;J. Lynch;David LeBauer;A. Millar;M. Stitt;S. Long

The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

拟南芥框架模型版本 2 预测生物钟基因失调的生物体水平影响

• DOI: 10.1101/105437
• 发表时间: 2017
• 作者: Chew Y