Hunting Down the Eagle Killer – Investigations into the Cyanotoxin Causing Avian Vacuolar Myelinopathy

追捕鹰杀手 â 调查引起禽空泡性脊髓病的蓝藻毒素

• 批准号: 412224404
• 负责人: Professor Dr. Timo H. J. Niedermeyer
• 金额: --
• 依托单位: Abteilung Pharmazeutische Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/412224404?language=en
• 关键词: Hunting; Down; Eagle; Killer; Investigations

Avian Vacuolar Myelinopathy (AVM) is a fatal neurological disease of birds observed with an increasing frequency in the south-eastern United States. Its alarming spread during the last 25 years has raised concerns about avian populations, including the iconic bird of prey, the bald eagle. All evidence points at AVM being caused by a novel cyanobacterial toxin that is produced by cyanobacteria of the novel species and genus Aetokthonos hydrillicola, growing epiphytic on aquatic plants and travelling up the food chain, finally causing the typical brain lesions observed in AVM affected birds.We could isolate the toxigenic cyanobacterium and bring it in culture. The compound that is most likely causing AVM has been isolated and its structure has been elucidated. The aims of the presented project are - to finalize the structure elucidation of the putative cyanotoxin, and to confirm if it is indeed the agent causing AVM,- to sequence the cyanobacterial genome, to identify the biosynthesis gene cluster of the compound, and to characterize the biosynthesis in more detail,- to study the factors driving toxin biosynthesis and its kinetics, assess the water composition of affected lakes, and characterize the interaction between host plants and the cyanobacterium,- to develop specific PCR/qPCR markers and protocols to routinely detect the cyanotoxin producers in environmental samples,- to study uptake and localization of the toxin in zebrafish, and - to characterize an additional cytotoxic compound produced by A. hydrillicola and to identify its putative biosynthesis gene cluster.The project thus contributes to - the understanding of the etiology of AVM, - the identification and bioactivity characterization of a novel cyanotoxin- the chemical characterization of a recently discovered cyanobacterial genus,- the elucidation of the biosynthesis of a structurally intriguing specialized metabolite,- the development of methods for the routine monitoring of the toxin and its producer.In order to be able to asses if the novel cyanotoxin might be a threat for freshwater ecosystems or even human health, it is mandatory to gain a better understanding of the cyanobacterial toxin, its production, the role it plays in inducing AVM, and its biological activity in general.The development of detection and monitoring techniques for this dangerous toxin is of a great importance for wildlife protection, water management, and environmental safety. Moreover, the chemical, biochemical, and molecular (genetic) data will provide important insights for natural product research, biotechnology, and synthetic biology. The potent bioactivity of the compound under study, its unique chemical structure, and its possible selective toxicity may offer a new scaffold for drug discovery and pharmaceutical research in the future.

禽类空泡脊髓病(AVM)是一种致命的禽类神经系统疾病，在美国东南部的发病率越来越高。它在过去25年中令人震惊的传播引发了人们对鸟类种群的担忧，包括标志性的猛禽--秃鹰。所有证据都表明，AVM是由一种新的蓝藻毒素引起的，这种毒素由新物种和属的蓝藻产生，生长在水生植物上，沿着食物链向上生长，最终导致AVM影响鸟类的典型脑损伤。我们可以分离产生毒素的蓝藻，并将其带到培养中。最有可能引起动静脉畸形的化合物已经被分离出来，其结构已经被阐明。本项目的目的是-最终确定推测的蓝藻毒素的结构阐明，并确认它是否确实是导致AVM的病原体-对蓝藻基因组进行排序，鉴定化合物的生物合成基因簇，并更详细地描述生物合成，-研究推动毒素生物合成的因素及其动力学，评估受影响湖泊的水组成，并表征宿主植物与蓝藻之间的相互作用，-开发专门的聚合酶链式反应/定量聚合酶链式反应标记和方案，以常规检测环境样本中的氰化毒素生产者，-研究毒素在斑马鱼中的吸收和定位，以及-表征由黑藻产生的另一种细胞毒性化合物，并鉴定其可能的生物合成基因簇。因此，该项目有助于-了解AVM的病因学，-鉴定和生物活性表征-新发现的蓝藻属的化学特性，-阐明结构上有趣的专门代谢物的生物合成，-发展常规监测毒素及其产生的方法。为了能够评估新的蓝藻毒素是否可能对淡水生态系统甚至人类健康构成威胁，必须更好地了解蓝藻毒素、其生产、以及人类健康这种危险毒素的检测和监测技术的发展对野生动物保护、水资源管理和环境安全具有重要意义。此外，化学、生化和分子(遗传)数据将为天然产品研究、生物技术和合成生物学提供重要的见解。所研究的化合物具有很强的生物活性，其独特的化学结构和可能的选择性毒性可能为未来的药物发现和药物研究提供一个新的支架。