Regulation of variable lifespan in castes of ants

蚂蚁种姓中不同寿命的调节

• 批准号: 8930039
• 负责人: Hua Yan
• 金额: $ 5.8万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8930039
• 关键词: Address; Adult; Aging; Aging-Related Process; Antioxidants; Ants; Behavior; Biological Process; Brain; Candidate Disease Gene; Castes; Cell Proliferation; Cells; ChIP-on-chip; ChIP-seq; Chromatin; Chromatin Structure; Coculture Techniques; Cues; Data; Down-Regulation; Drosophila genus; Epigenetic Process; Fat Body; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Gene Targeting; Genes; Genetic; Growth; Growth Hormone Receptor; Health; Histone H3; Histones; Homologous Gene; Human; Hydrocarbons; In Vitro; Individual; Insulin; Insulin-Like Growth Factor I; Larva; Longevity; Maintenance; Mitosis; Molecular Profiling; Organism; Ovarian Tissue; Ovary; Pattern; Peptides; Pheromone; Physiological; Play; Process; Production; Proteins; Regulation; Reproduction; Role; Signal Transduction; Somatic Cell; Staging; Staining method; Stains; Starvation; Testing; Time; Tissues; Transcription factor genes; Up-Regulation; Variant; base; differential expression; egg; feeding; fly; insight; insulin signaling; interest; novel; receptor; receptor expression; reproductive; response; transcription factor

DESCRIPTION (provided by applicant): Aging is an intrinsic process leading to the progressive decline in physiological functions. In response to environmental cues, genetically identical individuals in the ant species Harpegnathos saltator can switch to more than 5 times longer lifespan, with changes in reproduction and behavior. The worker to gamergate transition in the ant is analogous to cell de-differentiation and re-differentiation in somatic cell reprogramming, which involves critical changes in gene expression and chromatin structure. The fat body plays crucial roles in the physiological changes during the gamergate transition, including ovary activation, egg production and variation in pheromone (cuticular hydrocarbon) profiles. Therefore, tracking gene expression profiles in the fat body will help clarify how a worker switches to a gamergate and achieves longevity. The preliminary data of the fat body transcriptome shows interesting gene expression profiles in antioxidants, cell proliferation, pheromone synthesis and insulin signaling. The data is consistent with previous studies in other species, suggesting a common mechanism underlying longevity. I will first analyze the adult and larvae fat body transcriptomes and use fly genetics to study the biological functions of the differentially expressed genes (DEGs). Second, these DEGs also contain transcription factors (TFs), which play an important role in the initiation and maintenance of gene expression profiles in the fat body during the worker to gamergate transition. TFs with strong changes in the gamergate transition will be selected to identify their target genes using fly genetics and ChIP. In addition, I will search for the target genes of chromatin modifiers. Last, I will address how th fat body regulates ovary activation. The candidate gene IGF-1 is an insulin-like peptide (ilp) predominately expressed in the H. saltator fat body. Its function may be similar to Dilp6, which regulates ovary activation in Drosophila. To address the function of IGF-1, in vitro co-culture of the fat body and ovary will be performed. This effect will be tested immunohistochemically, using the cell mitosis marker phosphor-histone H3 (H3S10P). In addition, purified IGF- 1 protein will be directly added to the worker ovary culture followed by H3S10P staining to test for ovary activation. In summary, this project will address how longevity is achieved in the transition from non- reproductive workers to reproductive gamergates, and the role of the fat body in this transition. This study will provide novel insights into the regulatory mechanisms underlying longevity.

描述（申请人提供）：衰老是导致生理功能逐渐衰退的内在过程。在对环境的反应中，基因相同的Harpegnathos saltator蚂蚁个体可以通过繁殖和行为的变化而延长5倍以上的寿命。蚂蚁从工蚁到合体的转变类似于体细胞重编程中的细胞去分化和再分化，涉及基因表达和染色质结构的关键变化。脂肪体在交配门过渡期间的生理变化中起着至关重要的作用，包括卵巢激活、卵子产生和信息素（表皮碳氢化合物）谱的变化。因此，跟踪脂肪体中的基因表达谱将有助于阐明工人如何转向游戏门并实现长寿。脂肪体转录组的初步数据显示了在抗氧化剂、细胞增殖、信息素合成和胰岛素信号传导中有趣的基因表达谱。这些数据与之前对其他物种的研究一致，表明了长寿的共同机制。我将首先分析成虫和幼虫脂肪体转录组，并利用蝇遗传学研究差异表达基因（DEGs）的生物学功能。其次，这些deg还含有转录因子（transcription factors, TFs），在脂肪体从worker到gamergate的转变过程中，转录因子在基因表达谱的启动和维持中起着重要作用。选择在gamergate转变中有强烈变化的tf，利用果蝇遗传学和ChIP鉴定其靶基因。此外，我将寻找染色质修饰因子的靶基因。最后，我将谈谈脂肪体如何调节卵巢的激活。候选基因IGF-1是主要表达于H. saltator脂肪体的胰岛素样肽（ilp）。它的功能可能类似于Dilp6，在果蝇中调节卵巢的激活。为了解决IGF-1的功能，将进行脂肪体和卵巢的体外共培养。使用细胞有丝分裂标记物磷酸组蛋白H3 （H3S10P）进行免疫组织化学测试。另外，将纯化的IGF- 1蛋白直接加入工房培养中，进行H3S10P染色检测卵巢活化情况。总之，本项目将探讨如何在从非生殖工作者到生殖游戏者的转变中实现长寿，以及肥胖体在这一转变中的作用。这项研究将为长寿的调控机制提供新的见解。