Understanding and using microbial conductive nanowires

摘要 电子沿着G.硫还原蛋白丝，称为 微生物纳米线已被用来解释广泛的全球重要的氧化还原现象。的 这些纳米线卓越的电子传导能力已经在医学领域引起了极大的兴趣。 应用空间，例如用于构建生物相容性材料和生物传感器。十多年来，G。 硫还原菌纳米线被认为是细菌IV型皮利，这得到了许多间接遗传学和 生化观察最近，我们发现这些导电纳米线不是由IV型菌毛制成的。 相反，这些结构是一种聚合的多血红素c型细胞色素，OmcS，它从来没有被 以前的特点。OmcS细丝模型与已知的OmcS在GEOLOGY中的作用一致 呼吸，但我们的知识细胞色素附件仍然非常有限。本研究旨在解决 关于呼吸原核生物细胞色素丝的基本科学问题，以及应用我们的 医学领域的新发现。具体来说，我将：A）鉴定和表征新型细胞色素 通过生物信息学算法，随后通过显微镜验证，在细菌和古菌菌株中发现丝状体。 B）然后利用高分辨低温电子显微镜研究这些细丝的导电机制 显微镜（cryo-EM）和电导率测量。C）最后，基于这些对细胞色素的新见解， 我将创造一种新颖的设计，用于自组装导电纳米线。这些纳米线可以是 或者可以含有基于肽/蛋白质的自组装支架 核心与可溶性细胞色素附加到外表面。研究结果将促进我们对 细胞色素纳米线，以及产生自组装纳米线支架，其可以用于许多领域。 未来的生物医学应用

Abstract Long-range (>10 μm) transport of electrons along networks of G. sulfurreducens protein filaments, known as microbial nanowires, has been invoked to explain a wide range of globally important redox phenomena. The remarkable electronic conduction capability of those nanowires has sparked a great deal of interest in the medical application space, such as for building biocompatible materials and biosensor. For more than a decade, G. sulfurreducens nanowires were thought to be bacterial type IV pili, supported by many indirect genetic and biochemical observations. Recently we showed that these conductive nanowires are not made of type IV pilins. Instead, these structures are a polymerized multi-heme c-type cytochrome, OmcS, which have never been characterized before. The OmcS filament model is consistent with the known roles of OmcS in Geobacter respiration, but our knowledge of cytochrome appendages is still very limited. This study aims at addressing fundamental scientific questions about cytochrome filaments in respiring prokaryotes as well as applying our discoveries into the general medical field. Specifically, I will: A) identify and characterize novel cytochrome filaments in bacterial and archaeal strains, through bioinformatics algorithms followed by microscopic validation. B) Then I will study the conduction mechanism of these filaments by high resolution cryogenic electron microscopy (cryo-EM) and conductivity measurement. C) Finally, based on these new insights into cytochrome filaments, I will create a novel design for a self-assembled conductive nanowire. These nanowires may be derived directly from a novel cytochrome filament or may contain a peptide/protein based self-assembled scaffold core with soluble cytochromes appended to the outer surface. The results will advance our understanding of cytochrome nanowires, as well as generating self-assembling nanowire scaffolds that may be used in many future biomedical applications.