IBCST - Competitive Renewal of MSM: Multiscale Studies of Segmentation in Verterb

描述（由申请人提供）：这项竞争性更新扩展了5 R 01 GM 076692 -01脊椎动物胚胎分割的多尺度研究资助的成功工作（35篇已发表论文），以开发用于模拟鸡体节形成的多尺度模拟工具。当前提案的战略背景是将最初资助期间取得的多项成就统一为一个连贯的体节发生模型，并提供NIH领导的机构间建模和分析小组（IMAG）小型研讨会和主要研究者会议关于模型共享的主要建议，2007年4月11日至12日：“一个多尺度模拟技术的重点示范项目，它解决了发育生物学中一个明确的，具体的问题，其中包括在整个发育过程中具有重要意义的各种生物机制，统一的多尺度方法是必不可少的。“鸡的体节发生是一个很好的选择示范项目，因为它是很好的实验特征，需要模拟最基本的发育机制，并要求既统一现有的方法在多个尺度（在这种情况下，合并广泛使用的，开源软件包系统生物学模型（SBW）用于亚细胞建模和CompuCell 3D（CC 3D）用于多细胞建模到组织中，模拟环境（TSE））和开发的一些关键的附加软件组件的广泛用途，在发育生物学模拟和关键的生物医学领域，如癌症和血管研究。该提案利用了NIGMS最近在Glazier的1 R 01 GM 077138 - 01 A1和Sauro的1 R 01 GM 081070 - 01 A1下对软件基础设施开发的投资，这两项投资分别大大增加了CC 3D和SBW的范围（支持改进用户界面，以生成、执行和分析模型;增强的脚本-语言支持、测试和验证模块的开发、改进文档、培训材料和用户支持）不包括合并SBW/CC 3D的开发或并行化，也不包括具有生物学意义的示范项目的部署。公共卫生相关性：模拟胚胎发育过程中的细胞相互作用和潜在的分子机制可以在实验生物医学研究中发挥至关重要的作用，有助于解释实验结果，建议实验，预测实验结果，并加深对基本生物机制的理解，从而加快对疾病的理解和治疗策略的制定。成功完成所提出的研究计划将提高医疗机构和行业的参与度，以及他们在开发建模工具及其有效利用创造新药和治疗方法方面的互动。

DESCRIPTION (provided by applicant): This competitive renewal extends the successful work (35 published papers) funded under 5R01GM076692-01 Multiscale Studies of Segmentation in Vertebrate Embryos to develop multiscale simulation tools for the simulation of somite formation in chicken. The strategic context of the current proposal is to unify the multiple accomplishments achieved during the original funding period into a coherent model of somitogenesis and to deliver the primary recommendation of the NIH-led Interagency Modeling and Analysis Group (IMAG) Miniworkshop and Principal Investigator's Meeting on Model Sharing, April 11-12, 2007: "a focused demonstration project for multiscale simulation techniques, which addresses a well- defined, specific problem in developmental biology, which includes a variety of biological mechanisms of importance throughout development and for which a unified multiscale approach is essential." Chick somitogenesis is an excellent choice of demonstration project because it is well- characterized experimentally, requires simulation of most fundamental developmental mechanisms, and requires both the unification of existing methodologies at multiple scales (in this case merging the widely-employed, open-source software packages Systems Biology Workbench (SBW) for subcellular modeling and CompuCell3D (CC3D) for multicell modeling into a Tissue-Simulation Environment (TSE)) and the development of a number of key additional software components of broad utility in developmental-biology simulation and in critical biomedical areas such as cancer and vascular research. This proposal leverages the investment NIGMS has recently made in software infrastructure development under 1R01GM077138-01A1 to Glazier and 1R01GM081070-01A1 to Sauro, which, while they greatly increase the scope of CC3D and SBW separately (by supporting improved user interfaces for model generation, execution and analysis; enhanced scripting- language support, development of testing and validation modules, improving documentation, training materials and user support), do not cover the development or parallelization of a merged SBW/CC3D, or the deployment of a biologically-meaningful demonstration project. PUBLIC HEALTH RELEVANCE: Simulations of cell interactions and underlying molecular mechanisms during embryonic development can play a vital role in experimental biomedical research, help with the interpretation of experimental results, suggest experiments, predict experimental outcomes and lead to a deeper understanding of fundamental biological mechanisms, thus expediting the understanding of diseases and the development of treatment strategies. Successful completion of the presented research plan will improve the involvement of medical institutions and industry, and their interaction in the development of modeling tools and their effective use in the creation of novel drugs and treatments.