Yeast Genetics and Stress Response Genes-Biomedical

酵母遗传学和应激反应基因-生物医学

• 批准号: 6897642
• 负责人: PAUL RUSSELL
• 金额: $ 29.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6897642
• 关键词: Schizosaccharomyces pombe; arsenic; biological models; biological signal transduction; biomarker; cadmium; environmental toxicology; eukaryote; functional /structural genomics; fungal genetics; gene environment interaction; gene expression; gene mutation; genetic mapping; genetic regulation; genetic screening; genetic strain; genetic transcription; hazardous substances; hydrogen peroxide; immune response genes; immunogenetics; microarray technology; oxidative stress; protein protein interaction

DESCRIPTION (provided by applicant): This proposal describes genetic and biochemical studies that are aimed at developing a better understanding of the effects of hazardous chemicals on eukaryotic organisms. The investigators want to decipher how eukaryotes sense hazardous chemicals and how they mount defensive responses. A central aim of these studies is to understand the signal transduction mechanisms that control gene expression in response to exposure to toxic chemicals. This type of knowledge will be crucial for understanding the effects of toxic chemicals on human health. A critical long-term goal of these studies will be the development of new strategies to improve detection of environmental toxins. Arsenic and cadmium will be emphasized in these investigations, although hydrogen peroxide will also be used as an efficient and specific method of inflicting oxidative stress. The fission yeast Schizosaccharomyces pombe will be used as the experimental organism for these studies. Fission yeast has be valuable model system for studying basic features of genotoxic and cytotoxic stress response mechanisms that are conserved amongst most eukaryotes, including mammals and plants. In the last funding period the investigators identified Csxl, a novel RNA-binding protein that controls global patterns of gene expression in response to oxidative stress In the upcoming funding period we propose to further these studies and to expand our area of investigation to include a functional genomics screen of genes whose expression is regulated in response to cadmium and arsenic exposure. They also plan to develop yeast strains that have arsenic and cadmium induced genes fused to readily detectable biomarkers. The project has three Specific Aims: 1) to understand how Csxl controls gene expression in response to oxidative stress. Csxl controls mRNA turnover during oxidative stress. All the mRNAs will be defined that are directly regulated by Csxl and investigate Cip1 and Cip2, two Csxl-interacting proteins. that play important roles in controlling gene expression in response to oxidative stress. The other Specific Aims are to 2) carry out a functional genomics screen to identify novel genes that play significant roles in tolerance of cadmium and arsenic, and 3) develop specific biomarkers for arsenic and cadmium.

描述（由申请人提供）：该提案描述了遗传和生化研究，旨在更好地了解危险化学物质对真核生物的影响。研究人员希望解读真核生物如何感知危险化学物质以及如何实现防御反应。 这些研究的一个核心目的是了解控制基因表达的信号转导机制，以响应暴露于有毒化学物质。这种类型的知识对于理解有毒化学物质对人类健康的影响至关重要。 这些研究的重要长期目标是开发改善环境毒素检测的新策略。 尽管过氧化氢也将用作造成氧化应激的有效且具体的方法，但在这些研究中将强调砷和镉。裂变酵母裂菌酵母POMBE将用作这些实验生物 研究。 裂变酵母是研究遗传毒性和细胞毒性应激反应机制的基本特征的宝贵模型系统，这些特征在包括哺乳动物和植物在内的大多数真核生物中保守。 在上一个资金期间，研究人员确定了CSXL，这是一种新型的RNA结合蛋白，在即将到来的资金期内，我们建议对氧化应激的全局模式控制基因表达的全局模式，以进一步进一步进行这些研究，并扩大我们的研究领域以包括对基因的功能基因组学筛查，其基因的功能基因组筛查受到对cadmium and cadmium and arsesenic ebalsenic and sensenic and sensenic exenic and sansency earsenic eactor的调节。他们还计划开发酵母菌菌株，这些酵母菌菌株具有砷和镉诱导的基因，可容易检测到可检测到的生物标志物。 该项目具有三个特定的目的：1）了解CSXL如何控制基因表达对氧化应激。 CSXL控制氧化应激期间的mRNA转换。 将定义所有由CSXL直接调节的mRNA，并研究CIP1和CIP2，两个CSXL相互作用的蛋白。那在控制基因表达中起着重要作用 对氧化应激的反应。另一个具体目的是2）进行功能性基因组学筛选，以鉴定新的基因，这些基因在镉和砷的耐受性中起着重要作用，以及3）为砷和镉开发特定的生物标志物。