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

从模式生物到模式进化枝：器官间通讯网络的可塑性和进化

• 批准号: RGPIN-2021-04399
• 负责人: Rajakumar, Rajendhran
• 金额: $ 2.99万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745587
• 关键词: Model; Organism; Clade; Plasticity; Evolution

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.

在自然界中观察到的发育和生理变化不仅仅是基因差异的结果。现在大量数据表明，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。蚂蚁具有高度可塑性：在发育过程中，同一组基因可以通过环境线索和激素调节产生一系列替代表型。这在不同种姓的个体之间产生了巨大的差异，包括形态、繁殖和寿命的差异。例如，环境变化可能会产生只能存活几个月的小型不育工蜂，或能活到 50 年的大型超繁殖蜂王。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，发育中和成年的器官已经进化出构成器官间通讯网络的信号（例如小肽、激素和 miRNA）。我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。在开展这项工作的同时，我的实验室将使用遗传模型果蝇果蝇对这些信号进行详细的机制研究。通过共同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具有基本生物学重要性的新问题。我们特别提出了以下三个短期目标/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，以及随后如何导致信号中的种姓差异由发育中的器官分泌？ (2) 在成年期，蜂王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导？ (3) 在进化过程中，这些不同的发育和成年种姓轨迹是如何起源的，从而使得在蚂蚁中观察到形态和生理特征的巨大多样性。我们的方法高度整合结合了实地工作、系统发育学、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人和社会的各种生物学水平，并将强大的比较多物种“模型进化枝”方法（蚂蚁）与高分辨率机械模型生物方法（苍蝇）协同作用。总而言之，它将增进我们对器官间信号传导如何在发育、生理学和进化背景下不断变化的环境中介导生物体反应的了解。