Mechanisms of the Response to Hydrogen Sulfide

对硫化氢的反应机制

• 批准号: 8145715
• 负责人: Dana L Miller
• 金额: $ 23.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145715
• 关键词: Affect; Age; Aging; Aging-Related Process; Animals; Applied Genetics; Award; Biological; Biological Assay; Biological Process; Caenorhabditis elegans; Cells; Chromosomes, Human, Pair 11; Data; Data Analyses; Disease; Exhibits; Exposure to; Foundations; Genes; Genetic; Genetic Epistasis; Genetic Models; Genomics; Goals; Histocompatibility Testing; Homeostasis; Homologous Gene; Hydrogen Sulfide; Immune System and Related Disorders; Infection; Injury; Instinct; Instruction; Insulin; Invertebrates; Lead; Learning; Longevity; Mammals; Mediating; Mentors; Messenger RNA; Metabolic; Microarray Analysis; Modeling; Molecular; Molecular Genetics; Monitor; Mutation; Organism; Pathway interactions; Phase; Phenotype; Physiological; Postdoctoral Fellow; Predisposition; Psyche structure; Publications; RNA Interference; Research; Resistance; Role; Signal Pathway; Sum; Techniques; Testing; Training; Transgenic Animals; Work; age effect; base; career development; dietary restriction; environmental change; experience; gene function; improved; insight; interest; mitochondrial dysfunction; muscle degeneration; mutant; novel; polyglutamine; programs; protein aggregation; reproductive; research study; response; senescence; skills; tool; tumor

All organisms must maintain homeostasis in the face of changing environmental conditions to survive. Physiological changes associated with ageing decrease the capacity to maintain homeostasis, increasing susceptibility to disease, injury and infection. As a postdoc with Dr. Mark Roth, Dr. Miller found that hydrogen sulfide (H2S), which is naturally produced by animal cells, increases lifespan and thermotolerance in C. elegans. In mammals, H2S improves survival in changing conditions. Thus, H2S may have a conserved function to improve the ability to maintain homeostasis. The purpose of the proposed research is to elucidate the mechanistic basis by which H2S modulates lifespan in C. elegans. The first aim will test the hypothesis that H2S delays age-associated changes in C. elegans. These experiments will establish how H2S affects diverse biological processes in different tissue types. In the second aim, genes and pathways involved in the response to H2S will be identified. This work will utilize genetic tools developed by Dr. Miller as a postdoc. Mutant animals which express H2S-induced phenotypes will be characterized to determine whether they influence lifespan and/or other aging-associated phenotypes. Epistasis will be used to determine which act in concert with sir-2.1. In a complementary approach, 1 will evaluate the role of genes that, like sir-2.1, are required for H2S-induced changes. Finally, I will use a microarray approach to identify genes affected by H2S-induced changes and are correlated with increased lifespan. The proposed research will generate publications and preliminary data that will enable Dr. Miller to apply for an independent ROI research award within 24 months of her transition to independence.

所有的生物体都必须在不断变化的环境条件下保持体内平衡才能生存。 与衰老相关的生理变化降低了维持体内平衡的能力， 易受疾病、伤害和感染。作为马克·罗斯博士的博士后，米勒博士发现氢 硫化物（H2S），这是自然产生的动物细胞，增加寿命和耐热性的C。 优美的在哺乳动物中，H2S可以提高在变化条件下的生存率。因此，H2S可能具有保守的 功能，以提高维持体内平衡的能力。这项研究的目的是阐明 H2S调节C.优雅的第一个目标将检验假设 H2S延缓了与年龄相关的C变化。优美的这些实验将确定H2S如何影响 在不同的组织类型中有不同的生物过程。在第二个目标中，涉及基因和途径的基因， 对H2S的反应将被识别。这项工作将利用米勒博士作为博士后开发的遗传工具。 将对表达H2S诱导表型的突变动物进行表征，以确定它们是否 影响寿命和/或其它衰老相关表型。上位性将被用来确定哪一行为在 音乐会2.1在一种补充方法中，1将评估像sir-2.1这样的基因的作用 H2S引起的变化。最后，我将使用微阵列方法来识别受 H2S引起的变化，并与寿命延长相关。这项研究将产生 出版物和初步数据，使米勒博士申请独立的投资回报率研究奖 在她过渡到独立的24个月内。