Our faculty hold these EPR grants.
Cholesterol Crystalline Domain Function in Eye Lens: EPR Spin-Labeling Studies
The long-term objective of this proposal is to achieve a greater understanding of the function of cholesterol in fiber cell membranes.
PI: Candice S. Klug
Lpt protein-mediated transport of LPS
The major goal of this project is to gain insights into the mechanism of LPS transport across the periplasm of Gram-negative bacteria to enable rational antibiotic drug design. This will be accomplished through the study of LptA, LptC, and LPS using site-directed spin labeling EPR spectroscopy and other biophysical techniques.
Mechanism of Activation and Membrane Interactions of Pseudomonas Toxin ExoU
In this project biochemical and biophysical studies will be used to elucidate the molecular mechanism of activation for the phospholipase ExoU, with a long term goal of facilitating the development of novel inhibitors to reduce tissue damage or sepsis due to P. aeruginosa infection.
MPI: Candice Klug / Christopher Kristich
Conformation and Functional Dynamics of a Bacterial PASTA Kinase
Transmembrane kinases containing PASTA domains control critical processes in most Gram-positive pathogenic bacteria, including antibiotic resistance, toxin production, virulence, cell division, and bacterial viability. The research proposed here promises to reveal new insights into the mechanisms by which this family of kinases functions to coordinate biological adaptations to environmental stimuli. These insights will facilitate development of new treatments for infections caused by Gram-positive bacteria by defining new targets for innovative therapeutics with potentially unique modes of action.
PI: Michael Lerch
Regulation of β2-adrenergic receptor signaling by post-translational modifications
G-protein-coupled receptors are a large and diverse class of cell surface receptors responsible for regulating nearly every physiological process in the human body and are therefore important targets for drug development. In this project, we aim to elucidate the molecular basis for modulation of β2-adrenergic receptor signaling by two post-translational modifications (PTMs), glycosylation and palmitoylation, using a complementary combination of continuous-wave and pulsed electron paramagnetic resonance techniques and functional assays. By detailing the effects of these PTMs on the conformational landscape, the results from these studies will provide insight into the understudied yet critical role of these PTMs as regulators of receptor signaling, thereby increasing researchers' ability to rationally design drugs to achieve the desired therapeutic effect.
Upgrades to a Bruker Q-band E580 Pulse EPR Spectrometer
The research proposed here, which uses novel state-of-the-art enhancements to a biophysical spectroscopic technique to enable the study of protein structure and functional dynamics, will lead to a better understanding of the physiology of disease processes such as cardiovascular and pulmonary diseases; cystic fibrosis; diabetes; obesity; behavioral, neurological, and psychiatric disorders; Alzheimer’s disease; and cancer. This research will also contribute to the development of novel antibiotics and cancer therapeutic agents, and to the design of safer and more effective drugs targeting a broad spectrum of diseases. Additional avenues of research are expected to be uncovered once the success of the initially proposed projects is evident, fostering further opportunities for new interdisciplinary science.