Intellectual Merit: Molecular and genetic studies have shown that proteins work in multimeric complexes to direct cellular events, and that transcription factors, in particular, can use selective interactions to differentially regulate gene expression. Existing methods for detecting these interactions are limited in the information that they provide, usually because the method of detection is most appropriate for studies done in cell culture or in single-celled organisms. This project involves developing a transformative method to detect transient interactions among transcription factors within the nuclei of the cells of living animals. The project will use the model organism, Caenorhabditis elegans, a small multicellular worm commonly used for developmental and genetic studies. Fluorescence imaging will be used detect interaction between a transcription factor tethered to the nuclear membrane and a fluorescently-labeled partner. Proof-of-concept experiments will be carried out with known interactors and,once established, the method will be applied to discover novel interaction partners. The research is novel and potentially of high significance because it would allow unprecedented in vivo detection of interaction between transcription factors throughout the life cycle of an organism.
Broader Impacts: Undergraduate, Masters, and PhD students from Georgia State University, an ethnically and racially diverse urban institution, will participate in all aspects of this project. In addition to providing research training, this project will provide an international research experience for two college students. The project will also enhance the research infrastructure at Livingstone College, a historically black college, through a combination of summer research experiences for Livingston College faculty and students and academic year lectures/visits to Livingstone by Georgia State University faculty. Furthermore, a postdoctoral fellow will gain supervised and guided teaching experience in both undergraduate and graduate classrooms.
