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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=691463
• 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。大自然设计了几种光敏元件，蛋白质使用这些元件来捕获和利用其能量。其中一种感光元素是视网膜，维生素A的一种形式。视网膜结合蛋白被称为视紫红质，人类和动物使用它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，大多数真菌和微观藻类，也有视紫红质，但用于不同的目的。微生物视紫红质被用作光驱动离子转运蛋白、光门控离子通道、光开关酶和感光受体。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，神经元可以对光敏感并被光操纵，例如，作为视觉假体。*** 我们的团队在生物学，化学和物理学的交叉点工作，试图发现，生产和深入表征新型微生物视紫红质。我们将使用生物信息学来寻找新的微生物视紫红质基因的DNA材料来自各种环境来源（所谓的宏基因组）。我们将分析基因，一旦我们发现一个有趣的不寻常的目标，我们将在细菌或酵母中制造相应的新型视紫红质（以其未修饰和突变的形式）。然后，我们将使用尖端的生物物理和生物化学技术，包括几种先进的光谱学，来了解这些新型视紫红质的作用（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学、进化和生理学产生了许多新的见解，并产生了新的光遗传学工具。我们希望我们的研究将有助于这两个令人兴奋的方向。