Collaborative Research: Towards an Integrative Mechanistic Theory of Within-Host Disease Dynamics

合作研究：建立宿主内疾病动态的综合机制理论

• 批准号: 0342388
• 负责人: Yang Kuang
• 金额: $ 122.33万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0342388&HistoricalAwards=false
• 关键词: Collaborative; Research; Towards; Integrative; Mechanistic

AbstractAwards: DMS 0342388, 0342239, 0342325Principal Investigators: Yang Kuang, Val Smith, Marilyn S. SmithThis multi-campus team is studying processes within a singlebiological host that can be described by models inspired by ecologicalstoichiometry, the study of the balance of energy and multiplechemical resources (usually elements) in ecologicalinteractions. These concepts have been broadened by their extension tobiological stoichiometry, which has proven to be an important new lensthrough which we can view and understand complex biologicalinteractions. Within this general theory, the cycling and utilizationof energy and multiple nutrients by organisms and their constituentcells occupies a central position. With its emphasis on the flow ofelemental matter, such as carbon, nitrogen, and phosphorus,stoichiometric theory covers multiple biological scales. It alsoallows, via rigid physical and chemical constraints, the constructionof robust mechanistic and predictive models. Originally formulated andverified in the fields of limnology and plant ecology, biologicalstoichiometry has recently been applied at physiological scales tosuch diverse areas as organism development and tumor growth. In thisproposal we aim to synthesize and apply theoretical and empiricalapproaches to biological stoichiometry within the grand framework ofinternal disease. Recent headline-grabbing findings that connectnutritional factors to disease dynamics indicate there is anincreasing need for stoichiometry-based mathematical models ofinternal disease that track the effects of potentially limitingresources. The proposed work weaves together threads of theoreticaland experimental research. Our primary aim is the construction ofpredictive and verifiable theoretical models which can begin toexplicitly deal with the effects of stoichiometric interactions inwithin-host disease dynamics. Such models will be built in a modularfashion, starting with simple deterministic models, and thenprogressively adding stochasticity, spatial heterogeneity, andgenetics. At each step the models will be challenged, calibrated, andtested by in vitro laboratory experiments.The proposed work will have a broad impact in both science researchand education, and eventually in internal disease management andtreatment. Regarding the former, our research team is trulyinterdisciplinary, with group members in mathematics, theoreticalphysics, ecology, and biomedicine. Our collaborative efforts willprovide undergraduate and graduate students and junior scientists ofdiverse ethnic/racial backgrounds with first-hand educationalexperience in cross-disciplinary communication and exploration. Thecurrent proposal is a step towards new ways to understand disease,aiming to develop robust and experimentally calibrated mathematicaltheories of disease-host interactions that can be applied to a widevariety of diseases. We firmly believe that such theories have acentral role to play in present and future research. These grants forproposals submitted as a collaborative proposal from threeinstitutions are made under the Joint DMS/NIGMS Initiative to SupportResearch Grants in the Area of Mathematical Biology. This is a jointcompetition sponsored by the Division of Mathematical Sciences and theDirectorate for Biological Sciences at the National Science Foundationand the National Institute of General Medical Sciences (NIGMS) at theNational Institutes of Health.

AbstractAwards：DMS 0342388，0342239，0342325Principal研究者：Yang Kuang，Val Smith，Marilyn S. Smiththis Multi-campthis Thisthis Multi-Campus团队在单个生物学宿主中研究这些过程，这些过程可以由模型启发到能源和多种资源的启发，并通过对资源进行了启发（量表），这些过程启发了（通常是对资源的研究）。这些概念通过扩展的学术化学计量来扩展，事实证明，这是一个重要的新lens，我们可以查看和理解复杂的生物学互相。在这一一般理论中，生物体及其组成型的循环和利用能量和多种营养占据了中心位置。石化理论的重点是碳，氮和磷等流动，例如碳，氮和磷理论，涵盖了多种生物学量表。它还通过刚性的物理和化学限制来构造强大的机械和预测模型的建构。最初在羊水学和植物生态学领域进行了制定的验证，最近在生物尺度上应用了随着生物体发育和肿瘤的生长，生物学的化学计量已在生理尺度上应用。在此规定中，我们旨在将理论和经验方法综合到内部疾病的宏伟框架内的生物化学计量。 最近引人注目的发现与疾病动力学连接性因素的发现表明，基于化学计量的基于化学计量的内部疾病的数学模型的需求无需跟踪潜在限制逆转的影响。 提出的工作将理论和实验研究的线程编织在一起。我们的主要目的是构建预测性和可验证的理论模型，这些模型可以开始应对在宿主疾病动力学中的化学计量相互作用的影响。这样的模型将以模块化时尚的形式构建，从简单的确定性模型开始，然后增强了随机性，空间异质性和属性。在每个步骤中，模型将受到挑战，校准和经过体外实验室实验的测试。拟议的工作将对科学研究和教育都产生广泛的影响，最终将在内部疾病管理和治疗中产生广泛的影响。关于前者，我们的研究团队确实是学科，具有数学，理论生理学，生态学和生物医学的小组成员。我们的合作努力将在跨学科的交流和探索方面具有第一手教育的本科生和研究生和初级科学家的本科生和初级科学家。 Thecurrent提案是迈向理解疾病的新方法的一步，旨在发展可用于广泛疾病的疾病宿主相互作用的鲁棒和实验校准的数学理论。我们坚信，这种理论在当前和未来的研究中都可以发挥上心作用。这些赠款的供应商在三个规定的协作提案中提出，是根据DMS/NIGMS的联合倡议提出的，以在数学生物学领域进行支持。 这是由国家科学基金会的数学科学和生物科学学院的共同竞选公司赞助的，是卫生研究院的国家一般医学科学研究所（NIGMS）。