纳米材料氧化石墨烯（GO）具有广泛应用潜力，但其毒副作用与分子机理尚未完全解析。预实验结果提示，模式生物秀丽线虫mir-235可能通过靶向daf-12从而调控GO转运和毒性效应。鉴于此，我们关注mir-235/DAF-12是基于怎样具体分子机制调控GO在体毒性和转运的？为此，将分析秀丽线虫mir-235突变对GO转运和毒性的影响；在分析候选靶基因daf-12调节GO转运和毒性及其组织特异性活性的基础上，确认mir-235与daf-12的分子靶向关系；基于测序数据及实验验证确认参与调控GO毒性及转运的靶基因，并分析调控GO毒性与转运过程中daf-12与靶基因之间遗传关系以及daf-12靶向基因介导的信号通路；同时解析DAF-12在调控GO毒性及转运过程中是否经由胰岛素信号通路和TGF-β信号通路。本项目将揭示mir-235调控GO转运和毒性的分子机制，并可能提出新的GO毒性分子评价终点。

Graphene oxide (GO) has received the great scientific attentions and can be potentially used in many fields. However, meanwhile, the adverse effects of GO and the underlying molecular mechanisms are still largely unclear. Our preliminary experimental data suggest that daf-12, as a target gene of mir-235, may be involved in the regulation of toxicity and translocation of GO in C. elegans. Thus, we are interested in the elucidation of the underlying molecular mechanism for functions of mir-235/DAF-12 in regulating toxicity and translocation of GO in nematodes. For this aim, we will investigate the effects of mir-235 mutation on toxicity and translocation of GO. Based on the analysis of functions of DAF-12 in regulating toxicity and translocation of GO and the tissue-specific activities of DAF-12, we will confirm the targeted relationship between mir-235 and daf-12 during the control of GO toxicity and translocation. Moreover, based on the sequencing data and experimental confirmation, we will determine the molecular targets for daf-12 gene in regulating the toxicity and translocation of GO. Again, we will investigate the genetic relationships between daf-12 and its targeted genes and the signaling pathways mediated by the targeted genes of daf-12 during the regulation of toxicity and translocation of GO. At the same time, we will also examine whether DAF-12 may function through Insulin/IGF-I and/or TGF-β signaling pathways in regulating the toxicity and translocation of GO. This study will provide evidence to elucidate the molecular mechanism of mir-235 in regulating the toxicity and translocation of GO in nematodes and will be helpful for advising new molecular endpoints for GO toxicity assessment.