TOPAS - nBio, a Monte Carlo tool for radiation biology research

 描述（由申请人提供）：我们的目标是开发一个平台，以促进更深入地了解辐射物理，化学和生物学之间的相互作用在亚细胞水平，并促进放射生物学研究问题的跨学科工作。蒙特卡罗（MC）方法已经成功地用于模拟辐射的物理性质，从放射治疗患者的宏观剂量沉积到细胞尺度，以了解相对生物学效应。但是，目前没有工具提供 辐射的宏观和微观生物效应的精确建模，研究人员可以确定哪些相互作用或结构（器官，细胞和亚细胞结构，如DNA，RNA或细胞膜）是感兴趣的。此外，MC码几乎完全由研究物理学家使用，因为它们的使用需要对临床物理学家和生物研究人员来说通常太长的学习期。因此，我们建议建立在以前开发的MC平台（TOPAS，PArticle模拟工具），并通过物理和化学过程的详细建模，在多个层次上推进物理和生物学的理解。我们将通过将TOPAS扩展到纳米尺度并包括亚细胞组分的细胞间和细胞内信号传导和辐射响应来提供生物建模的新方法。这一建议将为更深入地了解辐射在组织中的生物效应奠定基础，以促进新的研究 在物理学和生物学的边界上。为此，我们将：SA1：自定义MC用于模拟荧光核径迹探测器（FNTD），并使用这些FNTD对模拟粒子径迹结构进行实验验证。 SA 2：促进自由基的化学追踪和MC内的亚细胞靶点（如DNA、RNA、膜、线粒体）响应模拟。 SA3：开发一个图形用户界面（GUI），并提供一个可扩展的亚细胞几何组件库，可以很容易地在研究人员之间交换。 战略领域4：制定具体的模型方案，在四个选定的研究主题中开展基础研究。由此产生的工具TOPAS-nBio将促进物理学家和生物学家之间的思想和结果交流。拟议的TOPAS-nBio的灵活性，加上研究人员之间开放的细胞成分交流，将促进跨领域的交流，为跨学科合作提供基础，并提供一种工具，以促进对辐射的生物反应的理解。

 DESCRIPTION (provided by applicant): Our goal is to develop a platform to contribute to deeper understanding of the interplay between radiation physics, chemistry and biology at sub-cellular levels and to facilitate interdisciplinary work on radiobiological research questions. Monte Carlo (MC) methods have been successfully employed to simulate physical properties of radiation, from the macroscopic dose deposition in radiation therapy patients down to the cellular scale to understand relative biological effectiveness. However, no tool currently provides accurate modeling of macroscopic as well as microscopic biological effects of radiation where researchers can define which interactions or structures (organ, cells and sub-cellular structures such as DNA, RNA or cell-membrane) are of interest. Furthermore, MC codes are nearly exclusively used by research physicists because their use requires a learning period that is generally too long for clinical physicists and biological researchers. We thus propose to build on a previously developed MC platform (TOPAS, a TOol for PArticle Simulation) and advance the physical and biological understanding across multiple levels through the detailed modeling of physical and chemical processes. We will offer a new approach to biological modeling by expanding TOPAS to the nanometer scale and include inter- and intra-cellular signaling and radiation response of sub-cellular components. This proposal will lay the foundation for a deeper understanding of the biological effects of radiation in tissues in order to facilitate new research at the boundary between physics and biology. To accomplish this we will: SA1: Customize MC for simulations of fluorescent nuclear track detectors (FNTD) and experimentally validate simulated particle track structures using these FNTDs. SA2: Facilitate chemical tracking of radicals and sub-cellular target (such as DNA, RNA, membrane, mitochondria) response simulation within MC. SA3: Develop a graphical user interface (GUI) and provide an extensible library of sub-cellular geometry components that can be easily exchanged among researchers. SA4: Develop specific model scenarios to carry out foundational research in four selected research topics. The resulting tool, TOPAS-nBio, will facilitate the exchange of ideas and results between physicists and biologists. The flexibility of the proposed TOPAS-nBio, together with open exchange of cell components among researchers, will facilitate communication across fields provide the basis for interdisciplinary collaborations and provide a tool to advance understanding of biological responses to radiation.