Realising the optogenetic potential of JellyOp: an opsin photopigment from the box jellyfish

实现 JellyOp 的光遗传学潜力：来自箱形水母的视蛋白感光色素

• 批准号: BB/K002252/1
• 负责人: Robert Lucas
• 金额: $ 47.24万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK002252%2F1
• 关键词: Realising; optogenetic; potential; JellyOp; opsin

The development of drugs that can influence physiology has played a crucial role in the huge advances in biological understanding that have occurred over the last century. However, this pharmaceutical approach to manipulating animal physiology has a number of well-known limitations. Drugs are commonly not very selective, having unintended effects on parts of the body, or physiological systems other than those of interest (so-called 'side effects'). Moreover, in comparison with the natural changes in physiology that they hope to regulate, drug effects build up rather slowly and persist for a long time. For these reasons, there would be a huge advantage in developing new ways of manipulating physiological systems that go beyond the achievements of pharmacy. We propose developing such a technology. Our approach will be to use a light sensitive version of a protein called a GPCR. GPCRs appear in practically every cell of our body. Their job is to fine tune the cell's activity and physiology according to signals released from neighbouring cells and other parts of the body. Because they are so influential they have long been recognised as a good way of treating the symptoms of disease. Indeed more than half of currently prescribed drugs are designed to alter their activity. By making photosensitive GPCRs we will be able to use light rather than drugs to tweak their activity. Unlike drugs, light can be switched on and off very rapidly. Light can also be applied at high doses to a single group of cells without influencing the rest of the body. These features mean that we will be able to use the new GPCRs to fine tune physiology with a resolution way beyond what is currently possible using drugs. This breakthrough will allow researchers to experimentally reproduce 'naturalistic' modulations in cell activity and examine their consequences. This is a great approach to understanding how the body works.

能够影响生理学的药物的开发在上个世纪发生的生物学理解的巨大进步中发挥了至关重要的作用。然而，这种操纵动物生理的药物方法有许多众所周知的局限性。药物通常不是很有选择性，对身体的某些部位或生理系统产生意想不到的影响，而不是那些感兴趣的（所谓的“副作用”）。此外，与他们希望调节的生理自然变化相比，药物作用的形成相当缓慢，持续时间也很长。由于这些原因，在开发操纵生理系统的新方法方面将有巨大的优势，这将超越药学的成就。我们建议开发这样一种技术。我们的方法是使用一种叫做GPCR的蛋白质的光敏版本。gpcr几乎存在于我们身体的每个细胞中。它们的工作是根据邻近细胞和身体其他部位释放的信号微调细胞的活动和生理。因为它们的影响很大，所以长期以来一直被认为是治疗疾病症状的好方法。事实上，目前超过一半的处方药都是为了改变其活性而设计的。通过制造光敏的gpcr，我们将能够使用光而不是药物来调整它们的活性。与药物不同，光可以非常迅速地打开和关闭。光也可以在不影响身体其他部分的情况下，以高剂量照射一组细胞。这些特征意味着我们将能够使用新的gpcr微调生理学，其分辨率远远超过目前使用药物所能达到的水平。这一突破将使研究人员能够通过实验再现细胞活动的“自然”调节，并检查其后果。这是了解身体如何运作的一个很好的方法。

项目成果

Additional file 9: of A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling

附加文件 9：GPCR 偶联的活细胞测定可识别用于控制 Go 和 Gi 信号传导的光遗传学工具

• DOI: 10.6084/m9.figshare.5793567
• 发表时间: 2018
• 作者: Ballister E

Additional file 4: Figure S3. of A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling

附加文件 4：图 S3。

• DOI: 10.6084/m9.figshare.5793525
• 发表时间: 2018
• 作者: Ballister E

Restoration of Vision with Ectopic Expression of Human Rod Opsin.

• DOI: 10.1016/j.cub.2015.07.029
• 发表时间: 2015-08-17
• 期刊: Current biology : CB
• 作者: Cehajic-Kapetanovic J;Eleftheriou C;Allen AE;Milosavljevic N;Pienaar A;Bedford R;Davis KE;Bishop PN;Lucas RJ
• 通讯作者: Lucas RJ

Optogenetic interrogation reveals separable G-protein-dependent and -independent signalling linking G-protein-coupled receptors to the circadian oscillator.

• DOI: 10.1186/s12915-017-0380-8
• 发表时间: 2017-05-15
• 期刊: BMC biology
• 影响因子: 5.4
• 作者: Bailes HJ;Milosavljevic N;Zhuang LY;Gerrard EJ;Nishiguchi T;Ozawa T;Lucas RJ
• 通讯作者: Lucas RJ

Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish.

• DOI: 10.1073/pnas.1721333115
• 发表时间: 2018-06-12
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Gerrard E;Mutt E;Nagata T;Koyanagi M;Flock T;Lesca E;Schertler GFX;Terakita A;Deupi X;Lucas RJ
• 通讯作者: Lucas RJ