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

这个项目将阐明离子和其他信号穿过膜相关蛋白通道的微观机制。研究人员将专注于参与这些过程的生物膜的动态和结构特征。最终，这些研究可能会为学习和记忆的理解带来新的见解。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。研究人员将聘请本科生和高中生谁没有历史上获得研究经验。该项目将为这些学生创造机会，在该国领先的研究机构进行尖端研究（例如，ORNL和BNL），从而激励了新一代的科学家。该项目将把联合收割机实验与数据分析和计算机模拟相结合。学生将提高他们的编程和实验室技能。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，这些技能将为学生申请学术界，研究机构和行业的职位提供优势。生物膜是由脂质双层和相关分子组成的高度复杂的结构。在这个项目中，研究人员的目标是研究来自脂质的力（FFL）原理的分子起源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（DIB）测量，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）全面了解离子通道活动的过程及其与刺激学习，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。通过控制嵌入膜中的成孔离子通道的活性，可以简单地通过控制离子穿过细胞膜的流动来操纵膜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具有根本的重要性。这个高风险、潜在变革性的项目旨在更大规模地在生物膜中的级联样松弛动力学（受FFL影响）和突触可塑性之间建立迄今未知的联系。该奖项反映了NSF的法定使命，并通过使用基金会的智力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.