Chemical and Structural Tools to Study Membrane Transport Proteins

New York University, New York NY

Investigators

Abstract

This project is jointly funded by the Chemical Measurements and Imaging Program in the Division of Chemistry in the Directorate of Mathematical and Physical Sciences and the Cellular Dynamics and Function Cluster in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences. Proteins are biomolecules used by the cell to carry out a wide range of essential functions. The two major protein classes are often differentiated by their water solubility. While extensive methods exist to study the structure and dynamics of water-soluble proteins, water-insoluble proteins that are found within the cell membrane (membrane proteins) offer unique challenges related to their native location within lipid bilayers. In this project investigators will develop a toolbox of experiments to characterize the structure and motions of membrane proteins on the atomic level. The results of these experiments will enable for a more fundamental understanding of this class of proteins and their essential roles in biology. The broader impacts include the participation of high school, undergraduate, and graduate students, which will disseminate knowledge in research at the interface of chemistry, biology, and physics. The principal investigator of the project will also co-develop a new laboratory approach to teach historically important experiments in biochemistry with the goal of increasing knowledge retention and achievement. Although the importance of membrane proteins have been well documented in signal transduction, molecular transport, and regulation of intracellular ion concentrations, less than 2% of known protein structures consist of these hydrophobic biomolecules. This research project will develop novel solid-state NMR techniques aimed at overcoming the major hurdles plaguing the characterization of membrane protein structure and dynamics. Specifically, the intellectual merits of this research include: (a) spectroscopic innovation aimed at improving the sensitivity and resolution of membrane protein spectra under native-like conditions in lipid bilayers, (b) new approaches to characterize the orientation of membrane proteins relative to the lipid bilayer, and (c) methods to study the mechanism of ion-coupled transport. The developments of this research will improve the feasibility of characterizing large, polytopic helical membrane proteins in lipid bilayers. The broader impacts of these research activities will be to (a) increase and disseminate knowledge in the interdisciplinary field of biophysical chemistry, (b) give research opportunities to and mentorship of high school and undergraduate students, and (c) emphasize the importance of clear and concise communication to promote science and technology. The PI's activities include the participation of undergraduate and high school students (e.g., ACS Project SEED, GSTEM, and School of the Future) from underrepresented groups in science and technology, including minorities, women, and those with disabilities. The involvement of young science-minded students in research is aimed at increasing retention and improving graduate rates in STEM fields. From an educational perspective, the PI will also take an active role in co-developing a Historical Experiments in Biochemistry lab course at Spelman College with Prof. Kimberly Jackson that will emphasize important experiments in the history of biochemistry. The outcomes of the project will be disseminated to the Faculty Resource Network at New York University with the goal of bolstering achievement in undergraduate teaching and biochemistry curricula across the 50+ member institutions.