权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Collaborative research: Signaling mechanisms in the crustacean molting gland

合作研究：甲壳动物蜕皮腺的信号机制

基本信息

批准号：
1922701
负责人：
Donald Mykles
金额：
$ 71.98万
依托单位：
Colorado State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1922701&HistoricalAwards=false
关键词：
Collaborative research Signaling mechanisms crustacean

项目摘要

Crabs, lobsters, and shrimp are ecologically and economically important crustaceans in marine environments. The hard, calcified exoskeleton provides protection and support, but restricts growth. As a result, these animals must periodically shed the exoskeleton, a process called molting. Upon molting, animals stretch the new exoskeleton before it hardens, providing more space for tissue growth. The entire process is controlled by molting hormone produced by a pair of molting glands. The activity of the molting gland is controlled by environmental signals mediated by the nervous system. Much remains to be known about the signaling genes that control the molting gland, in particular the genes required for (1) committing the animal to molt and (2) repressing the molting gland after the animal molts. Commitment is a “point of no return” decision that is critical for survival and growth in all crustaceans. Repression prevents molt induction until synthesis and calcification of the exoskeleton is completed. This collaborative project involves a team of investigators from four universities who will use state-of-art DNA and peptide sequencing technologies to identify genes and proteins essential for the activation, commitment, and repression of the molting gland and its regulation by environmental signals. The data generated will be made available to researchers so that they can better understand how to manage fisheries, develop effective aquaculture practices, and mitigate the effects of pollutants and climate change. Three postdoctoral fellows, four graduate students, and 6-8 undergraduates will receive training in advanced molecular techniques and bioinformatics. An educational outreach program for teachers recruited from junior high and high schools in northeastern Colorado will be developed.In crustaceans, paired molting glands (Y-organs or YOs) produce ecdysteroids necessary for systemic molt cycle control. Molt-inhibiting hormone (MIH), produced in the eyestalk ganglia, inhibits the synthesis of ecdysteroids by the YO via a putative G protein-coupled receptor (GPCR) and cyclic nucleotide second messengers. The project will use transcriptomic and proteomic tools to determine the signaling mechanisms that drive YO phenotypic changes over the molt cycle; these are designated basal in intermolt, activated in early premolt, committed in mid and late premolt, and repressed in postmolt. The specific aims are to: (1) determine how MIH signaling inhibits Mechanistic Target of Rapamycin (mTOR) activity; (2) determine the role of Transforming Growth Factor beta/Activin signaling in YO commitment; (3) determine the role of ecdysteroids on YO entry into, and exit from, the repressed state; and (4) characterize the MIH receptor. The first three aims will quantify the phenotypic effects of experimental signaling manipulations on YO state transitions. Network analysis of RNA-sequence and liquid chromatography-tandem mass spectrometry data will determine the effects of experimental treatments on gene interactions and downstream targets of signaling pathways. Aim #4 uses transcriptomic tools and a luciferase ligand/receptor binding assay with recombinant neuropeptides to characterize candidate GPCRs for receptor function. A thorough understanding of the hormonal regulation of decapod molting and growth is essential to manage fisheries, develop effective aquaculture practices, and mitigate potential effects of pollutants and environmental factors on an economically and ecologically important group of marine organisms. Three postdocs, four graduate students, and 6-8 undergraduates will receive training in advanced molecular techniques and bioinformatics, and a grade 6-12 teacher will be involved in educational outreach on the research topic.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

螃蟹、龙虾和虾是海洋环境中具有重要生态和经济意义的甲壳类动物。坚硬、钙化的外骨骼提供了保护和支撑，但限制了生长。因此，这些动物必须定期蜕去外骨骼，这一过程被称为蜕皮。在蜕皮时，动物在新外骨骼变硬之前拉伸它，为组织生长提供更多的空间。整个过程是由一对蜕皮腺产生的蜕皮激素控制的。蜕皮腺的活动受神经系统介导的环境信号控制。关于控制蜕皮腺的信号基因，特别是(1)使动物蜕皮和(2)在动物蜕皮后抑制蜕皮腺所需的基因，还有很多需要了解的。承诺是一种“无法回头”的决定，对所有甲壳类动物的生存和成长至关重要。抑制阻止蜕皮诱导，直到外骨骼的合成和钙化完成。该合作项目涉及来自四所大学的一个研究小组，他们将使用最先进的DNA和肽测序技术来识别对脱毛腺的激活、承诺和抑制以及环境信号对其的调节至关重要的基因和蛋白质。产生的数据将提供给研究人员，以便他们能够更好地了解如何管理渔业，制定有效的水产养殖做法，以及减轻污染物和气候变化的影响。3名博士后、4名研究生和6-8名本科生将接受高级分子技术和生物信息学方面的培训。为从科罗拉多州东北部的初中和高中招募教师，将制定一项教育推广计划。在甲壳类动物中，成对的蜕皮腺（y -器官或yo）产生蜕皮激素，这是控制系统蜕皮周期所必需的。在眼柄神经节中产生的脱毛抑制激素（MIH）通过假定的G蛋白偶联受体（GPCR）和环核苷酸第二信使抑制YO合成蜕皮甾体。该项目将使用转录组学和蛋白质组学工具来确定在蜕皮周期中驱动YO表型变化的信号机制；这些细胞在蜕皮过程中处于基部，在蜕皮早期被激活，在蜕皮中期和后期被激活，在蜕皮后被抑制。具体目的是：(1)确定MIH信号如何抑制雷帕霉素（mTOR）活性的机制靶标；(2)确定转化生长因子β /激活素信号在YO承诺中的作用；(3)确定外皮甾体在YO进入和退出抑制状态中的作用；(4)表征MIH受体。前三个目标将量化实验信号操作对YO状态转换的表型影响。rna序列的网络分析和液相色谱-串联质谱数据将确定实验处理对基因相互作用和信号通路下游目标的影响。Aim #4使用转录组学工具和重组神经肽荧光素酶配体/受体结合试验来表征候选gpcr的受体功能。深入了解十足动物蜕皮和生长的激素调节对于渔业管理、开发有效的水产养殖实践以及减轻污染物和环境因素对经济和生态重要的海洋生物群体的潜在影响至关重要。三名博士后、四名研究生和6-8名本科生将接受高级分子技术和生物信息学方面的培训，一名6-12年级的教师将参与研究课题的教育推广。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。