Marty Burke harnesses the power of synthetic organic chemistry to understand and maximize the capacity for small molecules to perform protein-like functions in the context of living systems. His research aims to enable the utilization of such small molecules as molecular prosthetics, i.e., replacements for proteins that are missing or dysfunctional in currently incurable human diseases.
Molecular Prosthetics: Replacing a Deficient Ion Channel Protein with a Small-Molecule Surrogate
Human diseases caused by an excess of protein function can often be treated effectively using small molecules that bind to the offending proteins and turn them off. In contrast, diseases caused by protein deficiencies are generally refractory to this approach. As a result, most of these diseases remain incurable with modern medicine. Our group therefore aims to advance the frontiers of pharmacology toward molecular prosthetics, i.e., functional small molecules that serve as substitutes for missing or dysfunctional proteins that underlie currently incurable human diseases.
This specific project aims to transform a naturally occurring small molecule called amphotericin B, which already can form ion channels in human cells, into a functional mimic of deficient protein ion channels that underlie currently incurable human diseases, such as cystic fibrosis. In this context, the student will have the opportunity to learn how to conduct a series of chemical and biophysical techniques, including small-molecule synthesis, liposome efflux assays, and planar lipid bilayer voltage-clamp recordings. Collectively, these studies stand to contribute to a better understanding of the inherent capacity for this natural small molecule to perform higher-order, protein ion channel-like functions in the context of living systems. Such molecules may also serve as valuable prototypes for a new generation of medicines that operate as prostheses on the molecular scale.