Genetics and biochemistry of surface structures of methanogenic archaea

包括产甲烷菌、极端嗜盐菌和各种嗜热和超嗜热生物在内的微生物群形成了一个进化上不同的第三生命领域，与细菌和真核生物分开。它们最初被认为只栖息在所谓的极端环境中。然而，今天，通过现代分子生物学技术，人们认为古生菌是世界性的，是各种全球循环的重要贡献者。此外，在许多不同的领域，包括生态学，生物技术，古菌对极端环境的适应，古菌作为真核生物过程的模型系统的使用，独特的古菌特异性特征，甚至古菌在人类疾病中的作用，都对古菌有着浓厚的研究兴趣。尽管它们的重要性显而易见，但由于许多原因，包括培养困难和普遍缺乏易处理的遗传系统，古细菌生理学，生物化学和遗传学的许多基本方面仍然研究得很差。在过去的二十年里，我的实验室已经开发了古生菌鞭毛作为模型系统，解决了许多这些问题。值得注意的是，我们已经证明，古细菌的鞭毛是一种独特的原核运动结构，与细菌的鞭毛有根本不同，而是更类似于细菌的另一种表面结构，即IV型皮利，其本身参与一种表面依赖性运动。我们建议继续和扩展我们的研究，确定更多的基因参与鞭毛的结构和装配，包括参与生物合成和连接的不寻常的聚糖鞭毛结构蛋白，一个重要的步骤，他们的装配。我们将鉴定各种必需鞭毛蛋白的物理相互作用，以帮助破译它们在鞭毛形成中的作用。我们将开始对另一种古细菌表面结构进行遗传研究，即皮利，我们最近再次证明，与任何已知的细菌皮利相比，它的结构是独特的。在继续研究这些真正独特的运动结构的结构，组装和遗传学的同时，我们还将继续推进基础古生物学的知识，包括蛋白质分泌和翻译后修饰等基本过程。

The Archaea, including methanogens, extreme halophiles and various thermophilic and hyperthermophilic organisms, form an evolutionarily distinct third Domain of life, separate from Bacteria and Eucarya. They were originally thought to inhabit only, so called, extreme environments. Today, however, through modern molecular biology techniques it is accepted that archaea are cosmopolitan and important contributors to various global cycles. In addition, there is strong research interest in archaea in many diverse fields including ecology, biotechnology, archaeal adaptations to extreme environments, the use of archaea as model systems for eukaryotic processes, unique archaeal-specific traits and even the role of archaea in human disease. Despite their obvious importance, for many reasons, including difficulty in cultivation and general lack of tractable genetic systems, many basic aspects of archaeal physiology, biochemistry and genetics remain poorly studied. Over the past two decades my lab has developed archaeal flagella as a model system which addresses many of these points. We have shown that, remarkably, the flagella of archaea are a unique prokaryotic motility structure, fundamentally different from bacterial flagella and instead more similar to another surface structure of bacteria, namely type IV pili, which themselves are involved in a kind of surface-dependent motility. We propose to continue and to extend our studies by identifying more genes involved in the structure and assembly of flagella including ones involved in the biosynthesis and attachment of the unusual glycan to flagella structural proteins, a step essential to their assembly. We will identify the physical interactions of various essential flagella proteins to help decipher their role in flagellation. We will begin genetic studies on another archaeal surface structure, namely pili, which we have recently demonstrated to be, again, unique in structure compared to any known bacterial pili. While continuing to examine the structure, assembly and genetics of these truly unique motility structures, we will also continue to advance the knowledge of basic archaeal biology including such fundamental processes as protein secretion and posttranslational modifications.