CAREER: Structure and Dynamical Mechanisms of Membrane Transport Proteins: New Vistas Via Ultra-stable Force Microscopy

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

Intellectual Merit In order for a cell to operate properly, some proteins must pass through membranes while other proteins must fold and insert themselves into membranes. How are these complex processes achieved at the molecular scale? What are the forces involved? How long does it take for the proteins to rearrange themselves? This research project aims to shed light on these issues by directly observing the arrangements and motions of individual proteins as they negotiate membranes. Techniques that are traditionally used in cellular studies have inherent challenges. As a result, there is little detailed knowledge regarding the complex molecular motions associated with these critical biological processes. The PI has developed and will employ a new tool- an ultra-high precision microscope- to directly study these interactions. This unique instrument, which is based on force, offers the potential to achieve atomically precise measurements of proteins and membranes in their natural state (in water at room temperature). These measurements, in conjunction with computer modeling and traditional biochemical experiments, will elucidate fundamental aspects of protein secretion and membrane protein folding. Broader Impacts The interface of molecular biology, nanotechnology and precision measurement provides a rich interdisciplinary medium that will broadly enhance the impact of this project. The educational and outreach activities of this project aim to address pressing needs across the educational spectrum, from elementary through graduate school to adult learning. These activities include: writing science education curriculum for a teacher training program aimed at improving elementary education in the state of Missouri; continued mentoring of high school and undergraduate students; creating incentives and training mechanisms to increase the impact of graduate student outreach activities; and entering direct dialogue with general audiences through interactive public speaking commitments. Collectively, these educational and outreach activities are designed to reach a broad range of individuals of all ages and backgrounds. Their overall objective is to promote scientific literacy and to convey the excitement of performing cutting edge scientific research.