In the human adrenal cortex, cortisol is synthesized in response to signaling cascades initiated by the trophic peptide hormone adrenocorticotropin (ACTH). The mechanisms by which ACTH directs cortisol production are multifaceted and include controlling the transcription of genes involved in steroidogenesis, regulating cholesterol (substrate) uptake and transport, modulating steroidogenic enzyme activity, and controlling electron availability. Although many of the molecular processes that underlie transcription of steroidogenic genes is well-established, post-translational mechanisms regulating the expression and activity of steroidogenic enzymes are less studied. Moreover, steroidogenesis is a multi-step process that occurs in two organelles, endoplasmic reticulum (ER) and mitochondria, yet the precise mechanism by which substrates are delivered back and forth between these two organelles is unclear. In this project, the PI will investigate the factors that control cortisol production in adrenal cells. Research will be carried out in two main areas. First, the PI will study the role of acetylation in controlling the protein expression of steroidogenic enzymes in mitochondria. The second objective is to identify and characterize the proteins that control the transport of intermediate steroid metabolites between ER and mitochondria. To achieve these goals, the PI will employ molecular, biochemical, and spectroscopic techniques such as confocal microscopy, site-directed mutagenesis, mass spectrometry, and enzyme activity assays. The studies outlined in this project will not only increase the understanding of the factors regulating steroid hormone biosynthesis, but also provide a training program for high school students and teachers, undergraduate and graduate students, as well as a postdoctoral researcher.
The primary focus of the research in this project is aimed at increasing an understanding of the processes that control cortisol production in the adrenal cortex. In addition to training graduate students and postdoctoral researchers in laboratory research, the PI will also mentor and train high school teachers by providing summer research internships. Each summer, a science teacher from a high school in the metropolitan Atlanta area will join the lab and carry out studies investigating the factors that control cortisol production. In addition to laboratory research, the teacher will also develop new modules that will be incorporated into his/her curriculum during the following school year. Through this partnership, graduate students will be afforded the opportunity to serve as mentors and high school students will be introduced to molecular and biochemical techniques. As in previous years, high school students will also spend time in the laboratory and the PI will visit the high school class periodically during the school year to discuss research and careers in science. Finally, the PI will continue to host undergraduate students year round. Like graduate students and postdoctoral researchers, the PI anticipates that the undergraduate students on the project will carry out independent research and disseminate their findings at national meetings and in peer-reviewed journals.
