Senior Honors Project
The CDC identifies heart disease as the leading cause of death in the U.S., and current treatments have variable success. Gene therapy is being investigated as an additional treatment option for heart disease. Various targets impacting calcium ion cycling and by consequence, cardiac contractility, are being studied as options for gene therapy. One molecular target in particular is the protein phospholamban (PLN), which is a small, hydrophobic protein located in the sarcoplasmic reticulum membrane of cardiac muscle, that has been linked to heart failure. Here, four PLN mutants were rationally designed, aiming for optimizing therapeutic potential. These mutants were analyzed using bioinformatics databases, and two of the mutants were successfully cloned, expressed, and purified. Results suggested these two mutants, R14E and Q26E, are predicted to fit the criteria for PLN therapeutic mutant design that were assessed. PLN mutants R14E and Q26E appear promising and further assessment of the impact and interaction of these mutants could offer insight into PLN’s role in heart failure, as well as provide potential targets for gene therapy.
Poss, Kristina R., "Heart Failure and Design of Potentially Therapeutic Mutants Relieving SERCA Inhibition: Expression and Analysis of Phospholamban Mutants" (2014). Antonian Scholars Honors Program. 44.