New functionalities of microbial rhodopsins - where bioinformatics meets biophysics

微生物视紫红质的新功能——生物信息学与生物物理学的结合

• 批准号: RGPIN-2018-04397
• 负责人: Brown, Leonid
• 金额: $ 5.03万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=646371
• 关键词: New; functionalities; microbial; rhodopsins; where

Many important processes in biology are driven by sunlight. Nature designed several light-sensitive elements used by proteins to catch and utilize its energy. One of these light-sensitive elements is retinal, a form of vitamin A. Retinal-binding proteins are called rhodopsins, which are used by humans and animals to perform one of the most important physiological functions - vision. Microbes, including various bacteria, some viruses, most fungi, and microscopic algae, have rhodopsins as well, but use them for different purposes. Microbial rhodopsins are used as light-driven ion transporters, light-gated ion channels, light-switchable enzymes, and photosensory receptors. Thus, these microbial rhodopsins are very important in bioenergetics and in all kinds of light-regulated microbial processes, including swimming and growth. They also have very interesting applications in neuroscience and biomedicine, via so-called optogenetics, where neurons can be rendered light-sensitive and manipulated by light, serving, for example, as visual prosthetics. *** Our group works at the intersection of biology, chemistry, and physics, trying to discover, produce, and characterize in depth novel microbial rhodopsins. We will use bioinformatics to look for new microbial rhodopsin genes in the DNA material derived from various environmental sources (so-called metagenomes). We will analyze the genes, and once we find an interesting unusual target, we will make the corresponding novel rhodopsin in bacteria or yeast (in their unmodified and mutated forms). Then we will use cutting-edge biophysical and biochemical techniques, including several kinds of advanced spectroscopy, to understand what these novel rhodopsins do (that is, their physiological functions) and how they do it (that is, the corresponding molecular mechanisms). This research approach has already yielded many novel insights into microbial ecology, evolution, and physiology, and also produced novel optogenetic tools. We are hopeful that our research will contribute to both of these exciting directions.

生物学中的许多重要过程都是由阳光驱动的。大自然设计了几种蛋白质用来捕捉和利用其能量的光敏元件。视网膜是这些光敏元件之一，是维生素A的一种形式。视网膜结合蛋白被称为视紫红质，人类和动物使用视紫红质来执行最重要的生理功能之一--视觉。微生物，包括各种细菌、一些病毒、大多数真菌和微小的藻类，也含有视紫红素，但它们的用途不同。微生物视紫红质被用作光驱动离子转运体、光门离子通道、光可切换酶和光敏受体。因此，这些微生物视紫红质在生物能量学和各种光调节微生物过程中都非常重要，包括游泳和生长。它们在神经科学和生物医学中也有非常有趣的应用，通过所谓的光遗传学，神经元可以变得对光敏感，并被光操纵，例如，用作视觉假肢。*我们的团队致力于生物学、化学和物理学的交叉，试图发现、生产和深入表征新型微生物视紫红质。我们将利用生物信息学在来自各种环境来源(所谓的元基因组)的DNA材料中寻找新的微生物视紫红质基因。我们将分析这些基因，一旦我们发现了一个有趣的不寻常的靶点，我们就会在细菌或酵母中制造相应的新型视紫红质(以其未经修饰和突变的形式)。然后我们将使用尖端的生物物理和生化技术，包括几种先进的光谱学，来了解这些新型视紫红素的功能(即它们的生理功能)以及它们是如何做到这一点的(即相应的分子机制)。这种研究方法已经对微生物生态、进化和生理学产生了许多新的见解，也产生了新的光遗传工具。我们希望我们的研究将为这两个令人兴奋的方向做出贡献。