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University of California-San Diego

Superfund Research Program

Yeast Genetics and Stress Response Genes

Project Leader: Paul Russell (The Scripps Research Institute)
Grant Number: P42ES010337
Funding Period: 2000-2017

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Project Summary (2005-2010)

This project is conducting genetic and biochemical studies that are aimed at developing a better understanding of the effects of hazardous chemicals on eukaryotic organisms. Dr. Russell and his research team are deciphering how eukaryotes sense hazardous chemicals and how they mount defensive responses. A central goal of these studies is to understand the signal transduction mechanisms that control gene expression in response to exposure to toxic chemicals. This type of knowledge is crucial for understanding the effects of toxic chemicals on human health. A critical long-term goal of these studies is to develop new strategies to improve detection of environmental toxins. Arsenic and cadmium are emphasized in these investigations, although hydrogen peroxide is also being used as an efficient and specific method of inflicting oxidative stress. The fission yeast Schizosaccharomyces pombe is being used as the experimental organism for these studies. Fission yeast has been a valuable model system for studying basic features of genotoxic and cytotoxic stress response mechanisms that are conserved amongst most eukaryotes, including mammals and plants. In the last funding period core researchers identified Csx1, a novel RNA-binding protein that controls global patterns of gene expression in response to oxidative stress.  In this funding period the researchers are furthering these studies and expanding their area of investigation to include a functional genomics screen of genes whose expression is regulated in response to cadmium and arsenic exposure. The team is also developing yeast strains that have arsenic and cadmium induced genes fused to readily detectable biomarkers. The project has three objectives:

  1. To understand how Csx1 controls gene expression in response to oxidative stress. Csx1 controls mRNA turnover during oxidative stress. The researchers are defining all the mRNAs that are directly regulated by Csx1 and investigating Cip1 and Cip2, two "Csx1-interacting proteins" that play important roles in controlling gene expression in response to oxidative stress.
  2. To carry out a functional genomics screen to identify novel genes that play significant roles in tolerance of cadmium and arsenic.
  3. To develop specific biomarkers for arsenic and cadmium.
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