Cause and Consequence of Transcription Errors in Biological Networks

点击翻译按钮获取中文摘要

Intellectual Merit: The information transfer from DNA to protein is not an accurate process; sometime errors in copying the information occur, resulting in the production of a malfunctioning protein. For proteins implicated in cellular differentiation programs, these errors have the potential to produce a heritable change in phenotype in genetically identical cells growing in the same environment. The overall goal of this research is to study the cause and the consequence of transcription errors on cellular differentiation programs using the bacterium Escherichia coli as a model organism. To capture and quantify transient transcription errors that lead to heritable phenotypic changes in genetically identical cells, a well characterized epigenetic switch, the lactose operon, will be used. Under specific conditions, the gene network of lac behaves like a differentiation system with two heritable outcomes that are susceptible to switching from one state to the next due to transcription errors. This research aims to identify novel genes involved in the avoidance of epigenetic switching and the physical alterations responsible for this epigenetic change. The results will provide new insights into the fine-tuning of genetic networks through transcriptional regulation.Broader Impact: Broader contributions of this project include training and teaching the next generation of scientists from high-school students to post-doctoral fellows, promoting scientific collaborations amongst international teams, and providing novel methods for studying the process of information transfer from DNA to protein that will be made publicly available. This research will be disseminated through peer reviewed journals and scientific meetings to inform the public of the role of the environment on epigenetic modification.