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

University Of Tennessee Knoxville, Knoxville TN

Investigators

Abstract

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.