Mechanisms of the Response to Hydrogen Sulfide

面对不断变化的环境条件，所有有机体都必须保持动态平衡才能生存。 与衰老相关的生理变化降低了维持体内平衡的能力，增加了 对疾病、伤害和感染的易感性。作为马克·罗斯博士的博士后，米勒博士发现氢 硫化物(H_2S)是由动物细胞自然产生的，它可以延长C。 优雅女装。在哺乳动物中，硫化氢提高了在不断变化的条件下的存活率。因此，硫化氢可能具有一种保守的 功能，提高维持动态平衡的能力。拟议的研究的目的是澄清 硫化氢调节线虫寿命的机制基础。第一个目标是检验这一假设 硫化氢延缓了线虫的年龄相关变化。这些实验将确定硫化氢如何影响 不同组织类型的不同生物学过程。在第二个目标中，基因和途径参与了 将确定对硫化氢的反应。这项工作将利用米勒博士开发的基因工具作为博士后。 将对表达硫化氢诱导表型的突变动物进行鉴定，以确定它们是否 影响寿命和/或其他与衰老相关的表型。上位性将被用来确定哪个动作 与SIR-2.1的音乐会。在一种互补的方法中，1将评估基因的作用，如SIR-2.1， 对于硫化氢诱导的变化是必需的。最后，我将使用微阵列方法来识别受 硫化氢引起的变化，并与延长寿命相关。拟议的研究将产生 出版物和初步数据，使米勒博士能够申请独立的ROI研究奖 在她过渡到独立的24个月内。

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.