Regulation of variable lifespan in castes of ants

描述(申请人提供)：衰老是一个内在的过程，导致生理功能的进行性下降。作为对环境线索的反应，在蚂蚁物种Harpegnathos saltator中，基因相同的个体可以延长5倍以上的寿命，并伴随着繁殖和行为的变化。蚂蚁从工蚁到配子门的转变类似于体细胞重编程中的细胞去分化和再分化，这涉及到基因表达和染色质结构的关键变化。脂肪体在配子门转换过程中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(角质碳氢化合物)的变化。因此，跟踪脂肪身体中的基因表达谱将有助于阐明工作人员如何切换到游戏门并实现长寿。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转导方面有趣的基因表达谱。这些数据与之前对其他物种的研究一致，表明了长寿背后的共同机制。我将首先分析成虫和幼虫的脂肪体转录本，并利用苍蝇遗传学来研究差异表达基因(Degs)的生物学功能。其次，这些DEG还含有转录因子(TF)，在工作者向配子门转变的过程中，转录因子在脂肪体基因表达谱的启动和维持中起着重要作用。在配子门转换过程中发生强烈变化的TFS将被选择使用苍蝇遗传学和芯片来识别它们的目标基因。此外，我还将寻找染色质修饰物的靶基因。最后，我将讨论脂肪体如何调节卵巢的激活。候选基因IGF-1是一种胰岛素样肽(ILP)，主要在跳鼠脂肪体中表达。它的功能可能类似于Dilp6，后者调节果蝇的卵巢激活。为了解决IGF-1的功能，将进行脂肪体和卵巢的体外共培养。这一效应将用细胞有丝分裂标志物组蛋白H3(H3S10P)进行免疫组织化学检测。此外，将纯化的IGF-1蛋白直接加入工人卵巢培养中，然后进行H3S10P染色，以检测卵巢的激活情况。总而言之，这个项目将解决如何在从非生殖工作者过渡到生殖游戏门的过程中实现长寿，以及肥胖身体在这一过渡中的作用。这项研究将为长寿背后的调控机制提供新的见解。

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.