Resolving the molecular mechanism of ion channels by novel FTIR spectroscopic approaches

探索我们大脑的奥秘，克服大脑疾病是中国大脑工程的中心目标。与脑功能相关的某些离子通道蛋白的结构和/或功能失效可诱发多种神经系统疾病。然而，由于对这种膜离子通道的结构和功能的认识不足，限制了对故障机制的理解。为了解决这一问题，我们的目标是在原子水平上解决膜电位对膜蛋白功能的影响。以膜蛋白感觉视紫红质II为例，我们能够通过表面增强红外吸收光谱（SEIRAS）证明外加电场如何影响膜蛋白单层的功能变化，这里是关键的质子转移步骤。这一成果是基于德国首席研究员Joachim Heberle和作为洪堡研究员访问德国的中国首席研究员Xiue Jiang之间的首次合作。目前的研究计划通过应用于对大脑功能至关重要的离子通道的细菌同源物，进一步建立在这种方法的基础上。将SEIRAS扩展到时域将允许在外加电场下跟踪通道门控的动态。最后，我们的目标是通过构建纳米粒子-膜离子通道蛋白混合系统来调节蛋白质的功能，这将为脑科学领域的紧迫科学问题提供新的见解。

Exploring the mysteries of our brain, and overcoming brain disease are the central aim of the China Brain Project. Failure in structure and/or function of certain ion channel proteins that are related to brain performance, can induce a variety of neurological diseases. However, the poor knowledge of the structure and function of such membrane ion channels limits the understanding of the mechanism of malfunction. To solve this issue, we are aiming to resolve the impact of the membrane potential on the functionality of membrane proteins on the atomistic level. Taking the membrane protein sensory rhodopsin II as an example, we were able to demonstrate by Surface-Enhanced Infrared Absorption Spectroscopy (SEIRAS) how an applied electric field affects the functional changes of a membrane protein monolayer, here a crucial proton transfer step. This achievement was based on the first collaboration between the German principle investigator (Joachim Heberle) and the Chinese principle investigator (Xiue Jiang), who has visited Germany as an Alexander von Humboldt Research Fellow. The present research proposal builds further on this methodology by the application to bacterial homologues of ion channels that are key to brain function. Extending SEIRAS to the time domain will allow for tracing the dynamics of channel gating under an applied electric field. Finally, we aim to modulate the protein functionality by constructing a nanoparticle-membrane ion channel protein hybrid system which will provide new insight into pressing scientific questions in the field of brain science.