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

探索大脑的奥秘，战胜大脑疾病，是中国大脑计划的中心目标。与脑功能相关的某些离子通道蛋白的结构和/或功能障碍可导致多种神经系统疾病。然而，对这种膜离子通道的结构和功能缺乏了解，限制了对故障机制的理解。为了解决这个问题，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，我们能够用表面增强红外吸收光谱(SEIRAS)演示外加电场如何影响膜蛋白单层的功能变化，在这里是一个关键的质子转移步骤。这一成果是基于德国首席调查员约阿希姆·赫伯勒(Joachim Heberle)和中国首席调查员(薛江)之间的首次合作，后者曾作为亚历山大·冯·洪堡研究员访问德国。目前的研究方案进一步建立在这一方法学的基础上，将其应用于对大脑功能至关重要的离子通道的细菌同源物。将SEIRAS扩展到时间域将允许跟踪在外加电场下的沟道选通的动态。最后，我们的目标是通过构建纳米颗粒-膜离子通道蛋白杂化系统来调节蛋白质的功能，这将为脑科学领域迫切的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.