Intellectual Merit: 'DNA codes for mRNA codes for Protein' is the well-established model of gene expression in cells. Recent evidence, however, suggests that the regulation of gene expression in our cells has many additional nuances that were not anticipated by this simple model. The amount of mRNA in the cytoplasm is known to be a product of both the rate of production of the mRNA (transcription) as well as the degradation rate of the mRNA. The underlying hypothesis for this research project is that there is a way for the status of the cytoplasmic mRNA to be communicated back to the nucleus and influence the rate of transcription. In other words, if the rate of degradation of a specific mRNA in the cytoplasm is increased, a signal can be sent back to the nucleus to increase the rate of synthesis (transcription), thus maintaining a steady-state level of the mRNA in the cytoplasm. Preliminary evidence has been obtained to suggest that this may well be the case and the goal of this research project is to formally test this hypothesis in proof of concept studies. The ability of an mRNA to send signals back to the nucleus to regulate its own synthesis is a novel idea that has fundamental bearing on how genetic information in cells is expressed. Thus a full understanding of this process has important implications in a variety of biological disciplines.
Broader Impacts: The research project brings together an interdisciplinary team that will result in the cross-training of both graduate students and postdoctoral level researchers. Such interdisciplinary training will provide an important skillset to these trainees for future career success. The project will strive to recruit underrepresented populations into the research endeavors to enhance scientific diversity. Data from the project will be incorporated into an advanced undergraduate/graduate course to give a broad set of students exposure to cutting-edge research. Outreach activities including posting on internet sites and meeting with high school students at science fairs, will raise public scientific literacy. Finally, the data, technology and models that are developed will be deposited in easily accessible databases and disseminated widely to promote the interdisciplinary incorporation of the potentially transformative ideas of the project.
