Multidimensional in vivo Assessments of Engineered Nanomaterials and Biological Interactions

工程纳米材料和生物相互作用的多维体内评估

• 批准号: 9352343
• 负责人: Robyn L Tanguay
• 金额: $ 21.63万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352343
• 关键词: Address; Adult; Animal Model; Animals; Behavior; Biological; Biological Assay; Biological Markers; Cardiovascular Physiology; Cell Death; Characteristics; Chemistry; Cognitive; Collaborations; Commerce; Complex; Consumption; Data; Development; Diet; Engineering; Environmental Exposure; Environmental Health; Environmental Impact; Exposure to; Future; Genetic; Goals; Growth; Health; Human; Human Microbiome; Inflammatory Response; Ingestion; Life; Materials Testing; Measures; Mitochondria; Modeling; Molecular; Morphology; Nanotechnology; National Institute of Environmental Health Sciences; Nature; Outcome; Oxidative Stress; Phenotype; Physiological; Physiology; Policy Maker; Property; Proteome; Research; Resources; Risk; Role; Safety; Scientist; Structure; Surface; Swimming; System; Testing; Time; Toxic effect; Translating; Uncertainty; Zebrafish; biological systems; biomaterial compatibility; cell type; gut microbiota; hazard; in vivo; in vivo Model; innovation; knowledge base; learning materials; materials science; mature animal; metabolome; microbiome; microbiota; multidisciplinary; nanomaterials; neurobehavior; neurobehavioral; novel; organ growth; rapid technique; response; screening; social; tool; transcriptome

While nanotechnology has significant potential to address critical societal needs, innovators, policy makers and the public have concerns that the novel properties of engineered nanomaterials (ENMs) may cause harm. The number of new ENMs being generated is outpacing our efforts to understand the impacts of these materials. To advance our understanding and to keep pace with new innovations, we increasingly need advances in ENM synthesis, characterization, and bioactivity screening. Due to the complexity of this challenge, highly interactive multi-disciplinary teams are needed. We will collaborate with the Nanomaterials Health Implications Research (NHIR): Engineered Nanomaterials Resource and Coordination Core (ERCC). We expect that the NHIR will provide precision-engineered, multifunction ENMs to probe the roles of surface chemistry and core characteristics in function and properties. We propose that zebrafish offer unparalleled advantages to broadly interrogate the interactions between ENMs and biological systems. It is now widely accepted that data collected using the zebrafish model is readily translated to humans because of the genetic and molecular conservation between these species. More importantly, the unique inherent advantages of this model provides research opportunities not possible or feasible in other systems. For example, with a small quantity of test material, it is possible to determine whether a given ENM is able to interact with biological targets to produce molecular changes in the transcriptome, proteome and metabolome within the entire animal. Sensitivity of these `omic approaches” is very high and uncertainty is reduced since all cell types are assessed simultaneously in the whole zebrafish. Additionally, changes in growth, organ development, cardiovascular function, and complex neurobehavior are easily assessed at a high throughput. Over the past several years, we have developed a number of novel tools and assays to assess the impacts of ENMs on adult zebrafish and the microbiome to further increase the sensitivity of our multi-dimensional screens. In this proposal we will rapidly evaluate the bioimpacts of the provided materials using multi-dimensional, high throughput early life stage and adult zebrafish bioassays that we have pioneered. We will rapidly provide these comprehensive response profiles to the NHIR consortium. We will complete the following specific aims: 1) Define a comprehensive biological response profile produced by exposure to ENM using early life stage zebrafish; 2) Determine the long lasting impacts of early life stage exposure to ENMs; 3) Evaluate the impact of ingestion of ENMs on the microbiota in adult zebrafish; 4) Integrate ENM responses from the zebrafish and other biological systems to develop principles to reduce hazards. We expect that with completion of these proposed studies and through interactions and collaborations with the NHIR consortium, the expanded knowledge base of ENM-biological interactions will begin to reduce the uncertainty around ENM health risks. In so doing, we will progress toward the longer term goal to maximize the benefits and minimize the negative impacts of ENMs.

尽管纳米技术具有满足关键社会需求的巨大潜力，但创新者，政策制定者和 公众担心工程纳米材料（ENM）的新型特性可能造成伤害。这 正在生成的新ENM数量超过了我们为了解这些材料的影响的努力。到 促进我们的理解并与新的创新保持同步，我们越来越需要ENM的进步 合成，表征和生物活性筛选。由于这一挑战的复杂性，高度互动 需要多学科团队。我们将与纳米材料的健康影响研究 （NHIR）：设计的纳米材料资源和协调核心（ERCC）。我们希望NHIR会 提供精确设计的多功能ENM，以探测表面化学和核心的作用 功能和属性的特征。我们建议斑马鱼提供无与伦比的优势 询问ENM与生物系统之间的相互作用。现在已经广泛接受了收集的数据 由于遗传和分子保护，使用斑马鱼模型很容易被翻译成人类 在这些物种之间。更重要的是，该模型的独特继承优势提供了研究 在其他系统中不可能或可行的机会。例如，使用少量测试材料，它是 可能确定给定的ENM是否能够与生物靶标相互作用以产生分子 整个动物中转录组，蛋白质组和代谢组的变化。这些'omic的敏感性 方法”非常高，不确定性降低，因为所有细胞类型均已在 整个斑马鱼。另外，生长，器官发育，心血管功能和复杂性的变化 神经行为很容易在高吞吐量中评估。在过去的几年中，我们已经开发了 新的工具和阿萨斯的数量，以评估ENM对成人斑马鱼和微生物组的影响 进一步提高了我们多维屏幕的灵敏度。在此提案中，我们将迅速评估 使用多维的高通量早期生命阶段和成人的生物影响 我们已经开创了斑马鱼生物测定。我们将迅速提供这些全面的响应概况 NHIR财团。我们将完成以下特定目的：1）定义全面的生物学 通过使用早期生命阶段斑马鱼暴露于ENM产生的响应曲线； 2）确定持久 早期生命阶段暴露于ENM的影响； 3）评估ENM摄入对微生物群的影响 成人斑马鱼； 4）整合斑马鱼和其他生物系统的ENM响应以开发 减少危害的原则。我们希望通过完成这些提议的研究以及通过 与NHIR联盟的互动和合作，ENM生物学的扩展知识基础 相互作用将开始减少ENM健康风险的不确定性。这样，我们将朝着 长期目标是最大化收益并最大程度地减少ENM的负面影响。