Predictive Multiscale Modeling of Microbial Consortia Biofilms

微生物群落生物膜的预测多尺度建模

• 批准号: 9123584
• 负责人: Ross P. Carlson
• 金额: $ 32.38万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9123584
• 关键词: Address; Antibiotic Therapy; Antibiotics; Bacteria; Bacterial Physiology; Behavior; Biological Models; Biomass; Cell Count; Cell surface; Cells; Chemicals; Chronic; Code; Communities; Complex; Computer Simulation; Computer software; Consumption; Data; Development; Diabetes Mellitus; Diffusion; Encapsulated; Environment; Environmental Engineering technology; Equation; Experimental Designs; Food Webs; Genes; Glucose; Goals; Growth; Health; In Situ; Individual; Interdisciplinary Study; Intervention; Kinetics; Knowledge; Lead; Length; Life; Link; Measurement; Measures; Medical; Metabolic; Methodology; Methods; Microbe; Microbial Biofilms; Modeling; Molecular; Nutrient; Obesity; Outcome; Phenotype; Physiological; Physiology; Planets; Polymers; Property; Proteome; Reaction; Reporting; Research; Review Literature; Software Tools; System; Talents; Testing; Therapeutic; Time; Toxic effect; Transcript; Translating; Ursidae Family; Variant; Work; analytical method; base; chronic wound; cost; design; energy balance; genome sequencing; genome-wide; killings; member; microbial; microbial community; microorganism; model development; multi-scale modeling; novel; organic acid; reconstruction; research study; response; three dimensional structure; tool

DESCRIPTION (provided by applicant): Biofilms are ubiquitous in medical, environmental, and engineered microbial systems. The majority of naturally occurring microbes grow as mixed species biofilms. These complicated biofilm consortia are comprised of a large number of cell phenotypes with complex interactions and self-organize into three-dimensional structures. While foundational to the vast majority of microbial life on the planet, the basic design principles of consortia biofilms are still poorly understood. We believe that a combination of computational and experimental tools is needed to address the challenge of characterizing, predicting and treating these complex systems. The overarching goal of this project is to develop an experimentally driven, predictive multiscale model that generates quantitatively accurate predictions of biofilm formation dynamics, species distributions and responses to perturbations. The biofilm model will be formulated by combining genome-scale metabolic reconstructions of individual species with reaction-diffusion equations for nutrient, metabolic byproduct and antibiotic transport through the biofilm. The biofilm model will be multiscale with respect to both time and length scales, with the metabolic models linking individual genes to cellular dynamics and the consortia model linking individual cells to community dynamics. The research will be developed using a medically relevant, three species chronic wound model system. Treatment of chronic wounds costs the US in excess of $25 billion per year and the costs are anticipated to grow rapidly due to the rise in diabetes and obesity. The specific aims of the proposed research are: (1) construct and evaluate a multiscale metabolic modeling framework for multispecies consortia biofilms in a dynamic, spatially resolved format; (2) develop and implement spatially resolved biofilm analytical methods to quantify physiologies of consortia and monoculture biofilms to inform and validate the computational model; and (3) predict and test spatially resolved metabolic responses to culturing perturbations including antibiotic treatments with iterative loops of hypothesis refinement. Expected outcomes of the proposed research are: (1) a general methodology and associated software tools for multiscale modeling of microbial biofilms to predict consortia dynamics in heterogeneous environments suitable for distribution to the multiscale modeling community; (2) experimental tools for spatially-resolved measurement of mass and energy balances within interacting consortia biofilms; (3) the first perturbation analysis of monoculture and multispecies chronic wound biofilms to nutrient variations and antibiotic treatments; and (4) proposed therapeutic strategies for effectively treating microbial consortia biofilms.

描述（由申请人提供）：生物膜在医学、环境和工程微生物系统中无处不在。大多数自然存在的微生物以混合物种生物膜的形式生长。这些复杂的生物膜联合体由大量具有复杂相互作用和自组织成三维结构的细胞表型组成。虽然这是地球上绝大多数微生物生命的基础，但人们对联合体生物膜的基本设计原则仍然知之甚少。我们认为，需要结合计算和实验工具来解决表征、预测和处理这些复杂系统的挑战。该项目的总体目标是开发一个实验驱动的、可预测的多尺度模型，该模型可以定量准确地预测生物膜形成动力学、物种分布和对扰动的响应。生物膜模型将通过将单个物种的基因组尺度代谢重建与营养物质、代谢副产物和抗生素通过生物膜运输的反应扩散方程相结合来制定。生物膜模型在这两个方面都是多尺度的