Collaborative Research: Multiscale Modeling of Solid Tumor Growth

合作研究：实体瘤生长的多尺度建模

• 批准号: 1155088
• 负责人: Vittorio Cristini
• 金额: $ 5.81万
• 依托单位: University of New Mexico Health Sciences Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-11-29 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1155088&HistoricalAwards=false
• 关键词: Collaborative; Research; Multiscale; Modeling; Solid

The goal of this project, which lies at the interface between mathematics and biology, is to develop mathematical models of tumor growth that connect intra-tumor molecular and cellular properties with critical tumor behaviors, such as invasiveness, and experimentally observable properties such as morphology. The research group will (1) perform novel analytical and computational studies of important constituent processes, (2) incorporate experimental data into these studies, and (3) develop and apply state-of-the-art numerical algorithms to large-scale computations over multiple time and space scales. By integrating experimental data with sophisticated, multi-scale mathematical and computational models, the potential for breakthroughs that will significantly further the understanding of tumor biology are great, thereby addressing a pressing national and global need. Solid tumors are complex micro-structured materials, where the three-dimensional tissue architecture (morphology) and dynamics are coupled in complex, nonlinear ways to cellular characteristics and to molecular composition and structure of the growth environment. This close connection between the tumor morphology and the underlying cellular/molecular dynamics has fundamental scientific importance in that the cellular dynamics that give rise to various tumor morphologies also control its ability to invade the host tissue. This allows observable properties of the tumor, such as its morphology, to be used to both understand the underlying cellular physiology and predict the tumors invasion potential. In particular, the conjecture that diverse morphologic patterns of invasion observed during tumor growth are the quantitatively predictable result of molecular inhomogeneity (of both composition and structure) in the tumors growth environment will be tested. Because tumor cells use similar or identical migration and proliferation mechanisms as normal cells, and because of the multi-scale nature of these processes, the mathematical modeling, analysis and simulation that will be conducted in this project will also have application in understanding normal functional processes during development, wound-healing, stem cell differentiation and tissue regeneration. This project will also establish a new collaboration among five institutions and broadens the participation of women and minorities in research as trainees in the investigators? groups, thereby addressing national needs. It will provide interdisciplinary training with theoreticians and experimentalists at the interface between mathematics and tumor cell biology. Finally, a month-long summer COSMOS (California State Summer School for Mathematics and Science) course at UC Irvine will be developed for high school students on these topics. This course enhances the participation of gifted high school students in research, and helps to recruit new math and science undergraduates, which addresses another national need.

该项目的目的是数学与生物学之间的界面，是开发肿瘤生长的数学模型，这些模型将肿瘤内分子和细胞特性与关键肿瘤行为（例如侵入性）以及实验性观察到的特性（如形态学）联系起来。研究小组（1）将对重要组成过程进行新的分析和计算研究，（2）将实验数据纳入这些研究，（3）在多个时间和空间量表上开发和应用最新的数值算法。通过将实验数据与复杂的，多尺度的数学和计算模型相结合，突破的潜力将大大进一步了解肿瘤生物学的理解非常好，从而满足了迫切的国家和全球需求。实体瘤是复杂的微观结构材料，其中三维组织结构（形态）和动力学以复杂的非线性方式耦合，用于细胞特征以及生长环境的分子组成和结构。肿瘤形态与潜在的细胞/分子动力学之间的这种紧密联系具有基本的科学重要性，因为引起各种肿瘤形态的细胞动力学也控制了其侵入宿主组织的能力。这允许可观察到的肿瘤的特性，例如其形态，可用于了解潜在的细胞生理学并预测肿瘤侵袭潜力。特别是，将测试猜想在肿瘤生长过程中观察到的侵袭的多种形态学模式是在肿瘤生长环境中分子不均匀（组成和结构）的定量预测结果。由于肿瘤细胞使用类似或相同的迁移和增殖机制与正常细胞一样，并且由于这些过程的多尺度性质，因此该项目将在该项目中进行的数学建模，分析和仿真也将在理解正常功能过程中在发育过程中的正常功能过程中应用。该项目还将在五个机构之间建立新的合作，并扩大妇女和少数群体作为研究人员的学员的参与？小组，从而满足国家需求。它将在数学和肿瘤细胞生物学之间的界面与理论家和实验者提供跨学科培训。最后，将为这些主题的高中生开发一个为期一个月的夏季宇宙（加利福尼亚州立大学数学和科学暑期学校）课程。本课程增强了有天赋的高中生研究的参与，并有助于招募新的数学和科学本科生，从而满足了另一种国家需求。