Genetics and biochemistry of surface structures of methanogenic archaea

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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.