Cause and Consequence of Transcription Errors in Biological Networks

智力优势：从DNA到蛋白质的信息传递不是一个精确的过程；有时在复制信息时发生错误，导致产生故障蛋白质。对于涉及细胞分化程序的蛋白质，这些错误有可能在相同环境中生长的基因相同的细胞中产生表型的可遗传变化。本研究的总体目标是利用大肠杆菌作为模式生物，研究细胞分化程序中转录错误的原因和后果。为了捕获和量化在基因相同的细胞中导致可遗传表型变化的瞬时转录错误，将使用一种特性良好的表观遗传开关，即乳糖操纵子。在特定条件下，lac的基因网络表现得像一个分化系统，具有两种遗传结果，容易由于转录错误而从一种状态切换到另一种状态。本研究旨在确定参与避免表观遗传开关和负责这种表观遗传变化的物理改变的新基因。该结果将为通过转录调控微调遗传网络提供新的见解。更广泛的影响：该项目的更广泛的贡献包括培训和教学从高中生到博士后研究员的下一代科学家，促进国际团队之间的科学合作，并为研究从DNA到蛋白质的信息传递过程提供新的方法，这些方法将公开可用。这项研究将通过同行评议的期刊和科学会议传播，使公众了解环境对表观遗传修饰的作用。

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.