CAS-Biophysical Studies of Lipid Droplets and their Associate Proteins

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Drs. Kerney Jebrell Glover, Nathan Wittenberg, and Wonpil Im from Lehigh University to investigate lipid droplets and the protein oleosin that is associated with lipid droplets. Lipid droplets are sphere-like entities found within cells that store energy for future use. Oleosin is a protein that is important to help stabilize these droplets in plant cells. The goals of this research are to use biochemical, biophysical, and computational methods better to study the structure of the oleosin protein and how it maintains the integrity of lipid droplets. Results from this study will be applied to explore the potential use of lipid droplets to remove pharmaceutical and personal care product pollutants from waterways. The project will provide research opportunities to undergraduate students and will develop a set of laboratory experiments in a capstone course for students to explore the use of lipid droplets to absorb environmental toxins.The objective of this research project is to understand the role that oleosin plays in lipid droplet homeostasis. Lipid droplets are quasi-spherical cellular entities that function as reservoirs of high-energy metabolites and consist of a triacylglycerol core encapsulated by a phospholipid monolayer that is punctuated extensively with the protein oleosin. The three-dimensional structure of oleosin will be modeled using a combination of NMR spectroscopy, Förster resonance energy transfer (FRET)-based fluorescent spectroscopy, and all-atom molecular dynamics simulations. Additionally, the mechanism by which oleosin prevents the coalescence of lipid droplets will be investigated through mutational studies. Finally, the ability of synthetic lipid droplets to act as pollution sequestration agents for the removal of pharmaceuticals and personal care products from waterways will be systematically investigated and optimized by varying the core polarity of the droplet. An important result of the proposed work will be the development of a ‘Membrane Builder’ extension to the graphical interface for the CHARMM molecular simulation program. This CHARMM-GUI will be made freely accessible to researchers who desire to run molecular dynamics simulations on lipid droplets.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.