EAGER: The Role of Lipids in Modulating the Synaptic Plasticity of Ion Channels

该项目将阐明离子和其他信号在膜相关蛋白通道中的传输的微观机制。研究人员将重点关注参与这些过程的生物膜的动态和结构特征。最终，这些研究可能会为理解学习和记忆带来新的见解。重要的是，该研究将利用橡树岭国家实验室（ORNL）和布鲁克海文国家实验室（BNL）等国家设施的强大资源，实施非侵入性散射技术来研究膜。调查人员将招募本科生和高中生，他们在历史上没有获得研究经验。该项目将为这些学生创造机会，在国内领先的研究机构（如ORNL和BNL）进行尖端研究，从而激励新一代科学家。这个项目将结合实验、数据分析和计算机模拟。学生将提高他们的编程和实验技能。这些技能对科学和工业都是必不可少的。学生将参加带薪暑期实习和/或论文项目。此外，这些技能将使学生在申请学术界、研究机构和工业界的职位时具有优势。生物膜是由脂质双分子层和相关分子组成的高度复杂的结构。本项目旨在研究脂质力的分子起源（FFL）原理及其在离子通道活性中的作用。他们将利用非侵入性散射技术，结合液滴界面双层（DIBs）测量，来研究这些分子机制。这些概念上遥远的技术将使研究人员能够在分子尺度上（通过散射）获得离子通道活动过程的全面图景，以及它与受刺激的学习、记忆和突触可塑性（通过dib）的关系。突触可塑性描述了由于突触之间的物理化学和机电活动而使学习和记忆成为可能的生物过程。通过控制嵌入在膜上的成孔离子通道的活性，人们可以通过控制离子在细胞膜上的流动来操纵膜的静息电位和其他信号。了解突触可塑性背后的详细的、多尺度的分子机制对于深入了解学习和记忆的分子基础至关重要。这个高风险的、潜在的变革性项目旨在在生物膜（受FFL影响）中级联式松弛动力学和突触可塑性之间建立迄今为止未知的联系。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project will elucidate the microscopic mechanisms involved in the transport of ions and other signals across membrane-associated protein channels. The investigators will focus on the dynamic and structural features of the biological membranes which are involved in these processes. Eventually, these studies may bring new insights into the understanding of learning and memory. Importantly, the study will implement non-invasive scattering techniques to study the membranes, leveraging the powerful resources at national facilities such as the Oak Ridge National Laboratory (ORNL) and Brookhaven National Laboratory (BNL). The investigators will engage undergraduates and high school students who do not historically have access to research experience. This project will create opportunities for these students to perform cutting-edge research at leading research facilities in the country (e.g., ORNL and BNL), thereby inspiring a new generation of scientists. This project will combine experiments with data analysis and computer simulations. Students will advance their programming and laboratory skills. These skills are imperative for both science and industry. Students will participate in a paid summer internship and/or thesis projects. Moreover, these skills will give students an advantage applying for positions in academia, research organizations, and industry. Biological membranes are highly complex structures consisting of a lipid bilayer and associated molecules. In this project the investigators aim to study the molecular origins of the force from lipids (FFL) principle and its role in the activity of ion channels. They will harness non-invasive scattering techniques, in conjunction with droplet interface bilayers (DIBs) measurements, to study these molecular mechanisms. These conceptually distant techniques will allow the investigators to get a comprehensive picture of processes involved in ion channel activity at the molecular scale (via scattering) and its relation to stimulated learning, memory, and synaptic plasticity (via DIBs). Synaptic plasticity describes biological processes that enable learning and memory due to the physicochemical and electromechanical activities between synapses. By controlling the activity of the pore-forming ion channels embedded in membranes, one can manipulate the membrane resting potential, and other signals, simply by controlling the flow of ions across the cell membrane. Understanding the detailed, multi-scale molecular mechanisms underlying synaptic plasticity are of fundamental importance in gaining insights into the molecular basis of learning and memory. This high-risk, potentially transformative project aims to make a hitherto unknown connection between the cascade-like relaxation dynamics in the biological membrane (influenced by the FFL) and synaptic plasticity on a larger scale.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.