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

描述（由申请人提供）：本次竞争性更新扩展了5R01GM076692-01脊椎动物胚胎多尺度分割研究的成功工作（35篇已发表论文），以开发用于模拟鸡体内体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所取得的多项成就统一为一个连贯的身体发育模型，并提供由nih领导的跨机构建模和分析小组（IMAG）迷你研讨会和2007年4月11日至12日模型共享首席研究员会议的主要建议。“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定义明确的具体问题，其中包括在整个发育过程中重要的各种生物机制，因此统一的多尺度方法是必不可少的。”鸡体发育是一个很好的示范项目，因为它在实验上有很好的特征，需要模拟最基本的发育机制，并且需要在多个尺度上统一现有的方法(在这种情况下合并广泛使用的，用于亚细胞建模的系统生物学工作台（SBW）和用于多细胞建模到组织模拟环境（TSE）的CompuCell3D （CC3D）的开源软件包，以及在发育生物学模拟和关键生物医学领域（如癌症和血管研究）中广泛应用的许多关键附加软件组件的开发。该提案利用了NIGMS最近在软件基础设施开发方面的投资，其中1R01GM077138-01A1为Glazier和1R01GM081070-01A1为Sauro，它们分别大大增加了CC3D和SBW的范围(通过支持改进的模型生成，执行和分析的用户界面；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/CC3D的开发或并行化，或部署具有生物学意义的示范项目。公共卫生相关性：胚胎发育过程中细胞相互作用和潜在分子机制的模拟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，提出实验建议，预测实验结果，并导致对基本生物学机制的更深入了解，从而加快对疾病的理解和治疗策略的制定。所提出的研究计划的成功完成将促进医疗机构和工业界的参与，以及它们在开发建模工具方面的相互作用，以及它们在创造新药物和治疗方法方面的有效利用。

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.