From Model Organism to Model Clade: Plasticity and Evolution of Interorgan Communication Networks

在自然界中观察到的发育和生理变异并不仅仅是基因差异的结果。现在有大量数据表明，基因和环境（营养、致癌物）共同产生了这种变异。蚂蚁是研究环境变化如何影响基因功能的新兴模型。蚂蚁具有高度的可塑性：在发育过程中，同一组基因可以通过环境提示和激素调节产生一系列不同的表型。这在不同种姓的个体之间产生了巨大的差异，从形态、繁殖和寿命的差异。例如，环境变化可以产生一个小的不育工蜂，只能活几个月，或者一个巨大的繁殖能力极强的蚁后，可以活50年。从昆虫到哺乳动物，为了确保生理状态反映环境的动态条件，发育和成年器官都进化出了组成器官间通信网络的信号（如小肽、激素和mirna）。我的实验室的研究目标是研究在发育和成年期间协调器官相互交流的分子信号，这对于产生种姓特异性变异至关重要。与此同时，我的实验室将利用遗传模型果蝇果蝇来研究这些信号的机制细节。通过综合利用新兴生物和模式生物，我的实验室将产生并解决具有高分辨率机制细节的基础生物学重要性的新问题。特别是，我们设定解决以下三个短期目标/问题：(1)在发育过程中，种姓特异性激素差异如何影响器官生长和形态发生的调节，以及随后这如何导致发育器官分泌信号的种姓差异？(2)在成年期，蜂后和工蜂之间生殖能力的巨大差异如何影响各种非生殖器官的功能和信号传递？(3)在进化过程中，这些不同的发育和成年种姓轨迹是如何产生的，从而使得在蚂蚁身上观察到的形态和生理特征的巨大多样性。我们的方法是高度整合田野调查，系统遗传学，功能基因组学，转录组学，发育遗传学，细胞和组织培养，以及先进的显微镜技术。我们还整合了从基因网络和细胞到个体和社会的各种生物学水平，并将一个强大的比较多物种“模型进化”方法（蚂蚁）与一个高分辨率的机制模型生物方法（苍蝇）协同。总之，它将推进我们对器官间信号如何在发育、生理和进化的背景下介导生物体在不断变化的环境中的反应的认识。

Developmental and physiological variation observed in nature, is not the result of differences in genes alone. A wealth of data now demonstrates that genes and the environment (nutrition, carcinogens) together generate this variation. Ants are an emerging model to investigate how environmental variation influences gene function. Ants are highly plastic: during development, the same set of genes can give rise to an array of alternative phenotypes through environmental cues and hormonal regulation. This generates dramatic differences between individuals of different castes, ranging from differences in morphology, reproduction, and longevity. For example, environmental variation can generate a small reproductively sterile worker that lives for a few months or a massive hyper-reproductive queen that can live up to 50 years. From insects to mammals, to ensure that physiological status reflects the dynamic conditions of the environment, developing and adult organs have evolved signals (ex. small peptides, hormones, and miRNAs) that comprise an interorgan communication network. The research goal of my laboratory is to investigate the molecular signals coordinating the intercommunication of organs during both development and adulthood, which are critical for generating caste-specific variation. In parallel to this work, my laboratory will investigate these signals in mechanistic detail using the genetic model fruit fly Drosophila melanogaster. Collectively by leveraging both emerging and model organisms, my laboratory will generate and tackle novel questions of fundamental biological importance with high-resolution mechanistic detail. In particular, we set out address the following three short-term objectives/questions: (1) During development, how do caste-specific hormonal differences influence the regulation of organ growth and morphogenesis, and subsequently how does this lead to caste differences in signals secreted by developing organs? (2) During adulthood, how do dramatic differences in reproductive capacity between queens and workers impact the functionality of, and signaling between, various non-reproductive organs? (3) During evolution, how have these divergent developmental and adult caste trajectories originated, enabling the vast diversity of morphological and physiological traits observed across ants. Our approach is highly integrative combining fieldwork, phylogenetics, functional genomics, transcriptomics, developmental genetics, cell and tissue culture, and advanced microscopy techniques. We also integrate various biological levels spanning from gene networks and cells, to individuals and societies, and will synergize a robust comparative multispecies `Model Clade' approach (ants) with a high-resolution mechanistic model organism approach (flies). Altogether, it will advance our knowledge of how interorgan signaling mediates the response of an organism in a changing environment in the context of development, physiology, and evolution.