Nano-response: Immune stimulation, microbiome perturbation, and impacts from protein corona

纳米反应：免疫刺激、微生物群扰动和蛋白电晕的影响

基本信息

批准号：
10018898
负责人：
Wenwan Zhong
金额：
$ 21.6万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018898
关键词：
Adsorption Aerosols Affect Air Pollution Alveolar Alveolar Macrophages Antigens Behavior Binding Biological Biological Assay California Capsid Proteins Carbon Carbon Nanotubes Cell Line Cell Survival Cells Chronic Collaborations Collection Cytoplasm Data Engineering Environment Environment and Public Health Environmental Engineering technology Environmental Exposure Epithelial Cells Exposure to Funding Gastrointestinal tract structure Gene Expression Goals Hazard Assessment Health Hispanics Immune Immune response Immune system Immunization Immunologist In Vitro Individual Inflammatory Inflammatory Response Ingestion Inhalation Institutes Intercellular Fluid Interdisciplinary Study Investigation Knowledge Liquid substance Liver Lung Mediating Metabolic Microbiology Mucous Membrane Mucous body substance Mus Nanotechnology National Institute of Environmental Health Sciences Particulate Particulate Matter Phagocytes Phenotype Physiological Positioning Attribute Production Property Protein Fingerprints Proteins Research Rodent Sampling Science Students Surface Surface Properties Sustainable Development Techniques Technology Testing Tissues Toxic effect Transgenic Mice Transportation Underrepresented Populations Volatile Fatty Acids Work advanced analytics alveolar epithelium base biological systems design environmental toxicology experimental study exposed human population exposure route gut microbiome immune activation in vivo interest intestinal epithelium microbial community microbiome microbiome alteration mouse model nano nanomaterials nanoparticle particle programs response titanium dioxide training opportunity trend uptake

项目摘要

PROJECT SUMMARY The increasing trend in human exposure to engineered nanomaterials (ENMs) calls for interdisciplinary researches to assess the biological impacts from nanomaterials and discover the fundamental factors that contribute to such impacts. We hypothesize that, the surface and other physicochemical properties of engineered nanomaterials (ENMs) affect adsorption of biomolecules like proteins, and the corona formed by the adsorbed biomolecules subsequently mediate interaction with biological systems. To test this hypothesis, our integrated study carried out by a team of chemists, immunologists, and environmental engineers will look at the effects of these interactions on activation of inflammatory and immune responses in tissues, as well as the effect on the dynamic microbial community in the gut. Our focus will be mainly on the interactions between environmental ENMs and mucosal tissues such as the airways and gut, where individuals will first encounter the ENMs; consequently, cellular interactions will also focus on lung alveolar macrophages and epithelium, intestinal epithelium, and mucosal immune tissues. We will also study the effects of chronic exposure on tissues in vivo using an environmental chamber. Three specific aims are incorporated into our research program: (1) To generate and characterize the corona-bearing ENMs for in vitro and in vivo study and dissect the relationship between corona formation and ENM's physicochemical properties; (2) To acquire the in vitro and in vivo toxicity and immune response profiles induced by corona-carrying ENMs and determine the impact of sub-chronic and chronic exposure to inhaled ENMs on cell and tissue responses to antigen; and (3) To analyze impacts from the corona-carrying ENMs on gut microbiomes. Our work will identify the protein fingerprints of the coronas formed in the exposure-relevant biological fluids, discover the correlation between corona composition and a collection of ENM properties, and reveal the biological responses from cells, tissues, and mice to the corona-carrying ENMs. Together, we will provide an integrated and comprehensive view of the biological and health impacts of nanomaterials in our environment. The long term goal of our work is to deliver knowledge that could help to predict the biological impacts of ENMs by their physicochemical properties.

项目概要人类接触工程纳米材料（ENM）的趋势不断增加，需要跨学科的研究研究评估纳米材料的生物影响并发现影响纳米材料生物影响的基本因素造成这种影响。我们假设，表面和其他物理化学性质工程纳米材料（ENM）影响蛋白质等生物分子的吸附，以及由其形成的电晕吸附的生物分子随后介导与生物系统的相互作用。为了检验这个假设，我们由化学家、免疫学家和环境工程师组成的团队进行的综合研究将寻找这些相互作用对组织中炎症和免疫反应激活的影响，以及对肠道动态微生物群落的影响。我们的重点将主要集中在之间的相互作用环境 ENM 和粘膜组织，例如气道和肠道，个体首先会遇到的地方 ENM；因此，细胞相互作用也将集中在肺泡巨噬细胞和上皮细胞上，肠上皮和粘膜免疫组织。我们还将研究长期暴露对使用环境室进行体内组织。我们的研究纳入了三个具体目标程序：(1) 生成并表征用于体外和体内研究和解剖的电晕 ENM 电晕形成与ENM理化性质之间的关系； (2) 获得体外以及携带电晕的 ENM 诱导的体内毒性和免疫反应特征，并确定其影响亚慢性和慢性暴露于吸入 ENM 对细胞和组织对抗原反应的影响； (3) 至分析携带电晕的 ENM 对肠道微生物组的影响。我们的工作将鉴定蛋白质在与暴露相关的生物体液中形成的电晕指纹，发现之间的相关性电晕成分和 ENM 特性的集合，并揭示细胞、组织、以及携带电晕的 ENM 的小鼠。我们将共同提供一个综合且全面的视图纳米材料对我们环境的生物和健康影响。我们工作的长期目标是交付有助于通过 ENM 的理化特性预测其生物学影响的知识。