SGER: Reverse Engineering Cellular Pathways from Human Cells Exposed to Nanomaterials-Development of Novel Risk Assessment Methods

SGER：对暴露于纳米材料的人体细胞进行逆向工程细胞途径 - 开发新型风险评估方法

• 批准号: 0436366
• 负责人: Mary Jane Cunningham
• 金额: --
• 依托单位: Houston Advanced Research Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0436366&HistoricalAwards=false
• 关键词: SGER; Reverse; Engineering; Cellular; Pathways

0436366 Cunningham The foundation for new and unique mathematical modeling and reverse engineering approaches to assess the toxicity of nanomaterials will be laid. Genomics, through the use of gene expression microarrays (GEM) will be used to evaluate samples from human epidermal keratinocytes (HEK) exposed to single-walled carbon nanotubes (SWNT) in culture. The data will be analyzed by statistical, similarity and predictive approaches as well as reverse engineered to determine the genetic regulatory networks which are involved. This research will set the stage for the ultimate goal of establishing new mathematical and engineering modeling methods to extrapolate the risk of nanomaterials to humans. Nanomaterials have been shown to have attributes, which far exceed the current traditional materials for medical, energy, and communications applications. Recently, however, several preliminary studies, but not all, have hinted that toxicity may be associated with nanomaterials. Most of these studies were performed on SWNT and using traditional toxicity assays. The research plan proposed here will use genomics to survey genes for indications of toxicity and will form the foundation for newly developed mathematical and reverse engineering algorithms to predict risk of exposure to human health. The novel and unique aspects of this research plan is the optimized experimental design as well as the comprehensive analysis scheme on the resulting data files, including reverse engineering of the genetic regulatory networks involved. This research will set the stage for the ultimate goal of establishing new mathematical and engineering modeling methods to extrapolate the risk of nanomaterials to humans.

0436366坎宁安将为评估纳米材料毒性的新的和独特的数学建模和逆向工程方法奠定基础。基因组学，通过使用基因表达微阵列（GEM）将被用来评估暴露于单壁碳纳米管（SWNT）培养的人表皮角质形成细胞（HEK）的样本。这些数据将通过统计、相似性和预测方法以及反向工程进行分析，以确定所涉及的遗传调控网络。这项研究将为建立新的数学和工程建模方法来推断纳米材料对人类的风险的最终目标奠定基础。 纳米材料已被证明具有远远超过目前传统材料的属性，用于医疗，能源和通信应用。然而，最近，一些初步研究（但不是全部）暗示，毒性可能与纳米材料有关。这些研究中的大多数是在单壁碳纳米管上进行的，并使用传统的毒性测定。 这里提出的研究计划将利用基因组学来调查基因的毒性迹象，并将为新开发的数学和逆向工程算法奠定基础，以预测暴露于人类健康的风险。这项研究计划的新颖和独特之处在于优化的实验设计以及对所得数据文件的综合分析方案，包括对所涉及的基因调控网络进行逆向工程。这项研究将为建立新的数学和工程建模方法以推断纳米材料对人类的风险的最终目标奠定基础。