University of Minnesota
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Transcription factor specificity environmentally-responsive gene regulatory networks                 

Posting expires on 03/21/2018

Research Site:
University of Minnesota - Duluth

Type of Research:
Basic Science

Department:
Biomedical Sciences

This opportunity does not have a stipend.

Description:
Oxidative stress is an early and ongoing contributor to most chronic diseases. 
The Cap-n-Collar (CNC) transcription factors are master regulators of the transcriptional response to oxidative stress, although the specific CNC protein regulating the type of response depends on the cell. Under basal conditions the activity of repressive CNC transcription factors dominates, and the activating CNC transcription factors prevail only when oxidative homeostasis is disrupted. We have used genome-wide chromatin immunoprecipitation (ChIP-seq) to begin identifying regions of the genome bound by CNC factors. We have found that Nrf1, Nrf2, and Bach1 target both the canonical cytoprotective genes as well as hundreds of unexpected, non-canonical genes. Interestingly, some of the non-canonical CNC target genes have important implications for human disease, and we are functionally evaluating these using luciferase reporter assays. The pharmaceutical industry has invested significantly in activators of Nrf2 as a way to induce CNC-regulated cytoprotective pathways, with the goal of treating chronic diseases. Our work suggests that CNC-mediated repression of non-canonical genes can also have important human health applications, and simply focusing on CNC-mediated transcriptional activation is shortsighted. Thus, we are assembling more comprehensive models of CNC regulatory networks to truly understand what happens when the activities of these transcription factors are altered, pharmacologically or genetically, in various disease states. Students will have opportunities to become familiar with basic lab techniques such as cell culture, cloning, electromobility shift assays, western blot, RNA, DNA, and protein isolation, PCR, and have the opportunity to learn more complex procedures such as protein purification and SELEX-seq. 

Please contact Matt Slattery (mslatter@d.umn.edu) or Sarah Lacher directly (selacher@umn.edu).


Posted on 03/21/2016