Genetics and biochemistry of surface structures of methanogenic archaea

古生菌，包括产甲烷菌、极端嗜盐微生物和各种嗜热和嗜热生物，形成了与细菌和真核生物不同的进化上截然不同的第三生命领域。它们最初被认为只居住在所谓的极端环境中。然而，今天，通过现代分子生物学技术，人们公认古生菌是世界性的，是各种全球循环的重要贡献者。此外，古生菌在许多不同的领域都有浓厚的研究兴趣，包括生态学、生物技术、古生菌对极端环境的适应、将古生菌用作真核过程的模式系统、古生菌特有的特征，甚至古生菌在人类疾病中的作用。尽管它们的重要性显而易见，但由于许多原因，包括栽培困难和普遍缺乏易于处理的遗传系统，古生物生理学、生物化学和遗传学的许多基本方面仍然缺乏研究。在过去的二十年里，我的实验室已经开发出古鞭毛作为一个模型系统，它解决了其中的许多问题。值得注意的是，古生菌的鞭毛是一种独特的原核运动结构，从根本上不同于细菌的鞭毛，而更类似于细菌的另一种表面结构，即IV型菌毛，它本身参与了一种表面依赖的运动。我们建议继续并扩展我们的研究，确定更多参与鞭毛结构和组装的基因，包括参与不寻常的葡聚糖的生物合成和附着到鞭毛结构蛋白的基因，这是组装它们的关键步骤。我们将确定各种基本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生菌表面结构的遗传学研究，即菌毛，我们最近再次证明，与任何已知的细菌菌毛相比，它在结构上是独一无二的。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本古生物生物学的知识，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.