BRC-BIO: Mechanistic regulation of dynamic gene expression patterns by temporal JNK activation

About This Grant

A fundamental feature of life is the ability to process information to initiate an appropriate response. This research project seeks to understand how cells interpret information related to stress. Understanding these processes is of significant importance to the scientific community by expanding our understanding of biology and testing this knowledge by building computational models of these processes. The approaches used to understand these mechanisms also have broader impacts beyond academic research alone. This includes providing training opportunities both for graduate and undergraduate students interested in careers in STEM fields, cross-disciplinary activities exposing high school students to the integration of data science and biology, and early elementary outreach to demonstrate how microscopy can be used to gain insight into cellular processes and foster interest in STEM. It is anticipated that the research will impact 100s of students over the duration of the project. Within this project, the investigators will examine the mechanisms that cells use to relay information through the stress kinase JNK and transcription factor c-Jun. Previous studies have shown that JNK activity is highly dynamic but it is unclear how this contributes to gene expression patterns. The investigators previously determined that different JNK dynamics can give rise to distinct gene expression patterns but it is unclear how these patterns are regulated. This project will focus on two mechanisms: 1) post-transcriptional regulation of genes through mRNA stability and 2) combinatorial regulation of genes by multiple transcription factors. The investigators will experimentally measure mRNA decay rates using metabolic labeling. Live-cell imaging of fluorescent reporters and mutation of 3’ UTR sequences will be used to determine how 3’ UTR sequences contribute to both mRNA stability and observed gene expression dynamics. For the second mechanism, the investigators will test how different promoter sequences and transcription factor binding sites contribute to dynamic gene expression over time to explore combinatorial gene regulation. Systematic deletions of cis-regulatory elements in fluorescent reporters will be used to assess impacts on gene expression dynamics over time. The collected data from objectives 1 and 2 will be used to refine a computational model of JNK signaling which will be used to facilitate future research into the function of JNK in cells. This project is jointly funded by the Established Program to Stimulate Competitive Research (EPSCoR), and the Division of Molecular and Cellular Biosciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.