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Functional analysis of insect neuropeptide G protein-coupled receptors.

昆虫神经肽G蛋白偶联受体的功能分析。

基本信息

批准号：
BB/P008097/1
负责人：
Shireen Davies
金额：
$ 108.36万
依托单位：
University of Glasgow
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP008097%2F1
关键词：
Functional analysis insect neuropeptide protein

项目摘要

To stay alive, organisms must continuously tune their various functions according to their internal and external environment. In multicellular organisms, the complex task of regulating the different tissues (lung, heart, liver, etc) is handled by chemical messengers (acetylcholine, insulin, etc) that bind to particular receptor proteins on, or in, the appropriate targets cells for such messages. In humans, the design of drugs that affect these receptors (GPCRs) - and thus alter the tuning of our bodies - is a huge area for the pharmaceutical industry, and major research programmes have given us some of the world's most widely used drugs for a range of disease (like high blood pressure or depression). Such GPCRs are no less important in insects, and as many of the world's most dangerous diseases (like malaria, dengue and Zika) are vectored by insects. With as many species as all other forms of life combined, it is inevitable that arthropods - and particularly insects - impinge on our lives in both positive and negative ways. They impact food security, both as pollinators and as destroyers of the world's crops; and also animal health, as vectors of animal and human disease. Climate change moves these threats ever closer to the UK, as evidenced by recent UK cases of blue tongue virus and the presence of alien insect crop pest species. Although there is a remarkable range of pesticides in use today to control insect pests, significantly, resistance to all classes of pesticides by insects is a serious problem, and few new insecticides have been brought to market in recent years. Furthermore, ever tighter regulatory controls require removal of useful compounds from our insect control repertoire. There is thus a need for a better understanding of insect physiology and environmental stress tolerance, so that we can identify new, more selective (and thus 'greener') ways of controlling them. As such, drugs impacting insect GPCRs have the potential to be new, more selective insect control agents. Here, we bring together a range of world-leading expertise and emerging technologies in this cross-disciplinary project between Life Sciences and Chemistry to address this issue. We will provide a deeper underdertanding of how these GPCRs signal in insects and also how they enable insects to withstand environmental stress for survival by developing new tools for use in an organismal context, based on the fruit fly, Drosophila melanogaster. We will also develop new small protein 'mimetics' which act on GPCRs (similar in function to the endogenous small proteins which activate GPCRs) that may be developed towards a new class of insect control agents which do not engender insect resistance, and which do not threaten the environment.

为了生存，生物体必须根据其内部和外部环境不断调整其各种功能。在多细胞生物体中，调节不同组织（肺、心脏、肝脏等）的复杂任务是由化学信使（乙酰胆碱、胰岛素等）处理的，这些信使与适当靶细胞上或靶细胞中的特定受体蛋白结合。在人类中，设计影响这些受体（GPCR）的药物-从而改变我们身体的调节-是制药业的一个巨大领域，主要的研究项目为我们提供了一些世界上最广泛使用的药物，用于治疗一系列疾病（如高血压或抑郁症）。这种GPCR在昆虫中同样重要，因为世界上许多最危险的疾病（如疟疾，登革热和寨卡病毒）都是由昆虫传播的。节肢动物的物种数量相当于所有其他生命形式的总和，因此，节肢动物--尤其是昆虫--不可避免地以积极和消极的方式影响着我们的生活。它们既作为授粉者又作为世界作物的破坏者，影响粮食安全;又作为动物和人类疾病的媒介，影响动物健康。气候变化使这些威胁越来越接近英国，最近英国发生的蓝舌病毒和外来作物害虫物种的存在就是证明。尽管目前使用的杀虫剂范围很广以控制昆虫害虫，但值得注意的是，昆虫对所有类别杀虫剂的抗性是一个严重的问题，近年来几乎没有新的杀虫剂进入市场。此外，越来越严格的监管控制要求从我们的昆虫控制库中去除有用的化合物。因此，有必要更好地了解昆虫生理学和环境胁迫耐受性，以便我们能够确定新的，更具选择性（因此“绿色”）的控制方法。因此，影响昆虫GPCR的药物有可能成为新的、更具选择性的昆虫控制剂。在这里，我们汇集了一系列世界领先的专业知识和新兴技术，在这个生命科学和化学之间的跨学科项目，以解决这个问题。我们将提供一个更深层次的理解，这些GPCR信号在昆虫中，以及它们如何使昆虫能够承受环境压力，通过开发新的工具，用于在生物体的背景下生存，基于果蝇，果蝇。我们还将开发作用于GPCR的新的小蛋白“模拟物”（在功能上类似于激活GPCR的内源性小蛋白），其可以被开发为一类新的昆虫控制剂，其不会产生昆虫抗性，并且不会威胁环境。