2022 Theses Doctoral

Developing and applying novel imaging methods for human diseases

Bekdash, Ramsey Azeez

Detailed in this thesis work are three distinct studies, each showcasing the development and use of imaging techniques to study physiological processes. In the first study, electrophysiology and fluorescence microscopy techniques are used to examine ion channel activity and endogenous protein-protein interactions to elucidate the mechanism through which dextromethorphan acts on the sigma non-opioid intracellular receptor 1 (SIGMAR1) to treat long QT syndrome.

The second study relates to the development and application of a novel genetically encoded metabolic indicator (GEM-IL). An in-depth characterization and comparison of GEM-IL to other fluorescent indicators is described and shows GEM-IL to be a reliable method for studying metabolic activity as demonstrated in vitro and in situ. Additionally, we have developed the first genetically encoded in vivo murine model for this indicator to facilitate further applications in metabolism study.

The last study reports on a novel method for the transient expression of SARS-CoV-2 envelope (E) protein in intracellular organelles and the plasma membrane of mammalian cells and Xenopus oocytes. Targeting the SARS-CoV-2 E protein to the plasma membrane allowed further study of the viroporin activity using fluorescence microscopy and electrophysiology techniques to allow for screening for new antiviral drugs to identify novel treatments for COVID-19.