The Unlimited Potential of Microbial Rhodopsins as Optical Tools

Microbial rhodopsins, a photoactive membrane protein
family, serve
as fundamental tools for optogenetics, an innovative technology for
controlling biological activities with light. Microbial rhodopsins
are widely distributed in nature and have a wide variety of biological
functions. Regardless of the many different known types of microbial
rhodopsins, only a few of them have been used in optogenetics to control
neural activity to understand neural networks. The efforts of our
group have been aimed at identifying and characterizing novel rhodopsins
from nature and also at engineering novel variant rhodopsins by rational
design. On the basis of the molecular and functional characteristics
of those novel rhodopsins, we have proposed new rhodopsin-based optogenetics
tools to control not only neural activities but also “non-neural”
activities. In this Perspective, we introduce the achievements and
summarize future challenges in creating optogenetics tools using rhodopsins.
The implementation of optogenetics deep inside an in vivo brain is the well-known challenge for existing rhodopsins. As a
perspective to address this challenge, we introduce innovative optical
illumination techniques using wavefront shaping that can reinforce
the low light sensitivity of the rhodopsins and realize deep-brain
optogenetics. The applications of our optogenetics tools could be
extended to manipulate non-neural biological activities such as gene
expression, apoptosis, energy production, and muscle contraction.
We also discuss the potentially unlimited biotechnological applications
of microbial rhodopsins in the future such as in photovoltaic devices
and in drug delivery systems. We believe that advances in the field
will greatly expand the potential uses of microbial rhodopsins as
optical tools.

微生物视紫红质，一类具有光活性的膜蛋白家族，作为光遗传学这一创新技术的基石，该技术通过光控制生物活动。微生物视紫红质在自然界中分布广泛，具有多样的生物学功能。尽管已知微生物视紫红质的种类繁多，但仅有少数被应用于光遗传学，以控制神经活动并理解神经网络。我们研究团队致力于从自然界中识别和表征新型视紫红质，并通过理性设计工程化新型变异视紫红质。基于这些新型视紫红质的分子和功能特性，我们提出了基于视紫红质的新型光遗传学工具，不仅可调控神经活动，还可控制‘非神经’活动。在本篇综述中，我们介绍了利用视紫红质创建光遗传学工具的成就，并总结了未来面临的挑战。将光遗传学深入到活体大脑内部是现有视紫红质面临的知名挑战。为了应对这一挑战，我们介绍了基于波前整形的光学照明创新技术，该技术可以增强视紫红质的低光敏感性，实现深部脑光遗传学。我们的光遗传学工具的应用可以扩展到操纵非神经生物学活动，如基因表达、细胞凋亡、能量产生和肌肉收缩。我们还讨论了微生物视紫红质在未来的潜在无限生物技术应用，例如在光伏器件和药物输送系统中。我们相信，该领域的发展将极大地拓展微生物视紫红质作为光学工具的潜在用途。