This proposal describes genetic and biochemical studies that are aimed at developing a better understanding of the effects of hazardous chemicals on eukaryotic organisms. The investigators want to decipher how eukaryotes sense hazardous chemicals and how they mount defensive responses. A central aim 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 will be crucial for understanding the effects of toxic chemicals on human health. A critical long-term goal of these studies will be the development of new strategies to improve detection of environmental toxins. Arsenic and cadmium will be emphasized in these investigations, although hydrogen peroxide will also be used as an efficient and specific method of inflicting oxidative stress. The fission yeast Schizosaccharomyces pombe will be used as the experimental organism for these studies. Fission yeast has be 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 the investigators identified Csxl, a novel RNA-binding protein that controls global patterns of gene expression in response to oxidative stress In the upcoming funding period we propose to further these studies and to expand our area of investigation to include a functional genomics screen of genes whose expression is regulated in response to cadmium and arsenic exposure. They also plan to develop yeast strains that have arsenic and cadmium induced genes fused to readily detectable biomarkers. The project has three Specific Aims: 1) to understand how Csxl controls gene expression in response to oxidative stress. Csxl controls mRNA turnover during oxidative stress. All the mRNAs will be defined that are directly regulated by Csxl and investigate Cip1 and Cip2, two Csxl-interacting proteins. that play important roles in controlling gene expression in response to oxidative stress. The other Specific Aims are to 2) carry out a functional genomics screen to identify novel genes that play significant roles in tolerance of cadmium and arsenic, and 3) develop specific biomarkers for arsenic and cadmium.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
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University of California San Diego
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Ahmadian, Maryam; Liu, Sihao; Reilly, Shannon M et al. (2018) ERR? Preserves Brown Fat Innate Thermogenic Activity. Cell Rep 22:2849-2859
Tapper, Elliot B; Loomba, Rohit (2018) Nonalcoholic fatty liver disease, metabolic syndrome, and the fight that will define clinical practice for a generation of hepatologists. Hepatology 67:1657-1659
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) Publisher Correction: The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:785
Zhang, Yuqin; Nasser, Victoria; Pisanty, Odelia et al. (2018) A transportome-scale amiRNA-based screen identifies redundant roles of Arabidopsis ABCB6 and ABCB20 in auxin transport. Nat Commun 9:4204
Tõldsepp, Kadri; Zhang, Jingbo; Takahashi, Yohei et al. (2018) Mitogen-activated protein kinases MPK4 and MPK12 are key components mediating CO2 -induced stomatal movements. Plant J 96:1018-1035
Li, Zixing; Takahashi, Yohei; Scavo, Alexander et al. (2018) Abscisic acid-induced degradation of Arabidopsis guanine nucleotide exchange factor requires calcium-dependent protein kinases. Proc Natl Acad Sci U S A 115:E4522-E4531
Hoffmann, Hanne M; Gong, Ping; Tamrazian, Anika et al. (2018) Transcriptional interaction between cFOS and the homeodomain-binding transcription factor VAX1 on the GnRH promoter controls Gnrh1 expression levels in a GnRH neuron maturation specific manner. Mol Cell Endocrinol 461:143-154
Zhong, Zhenyu; Liang, Shuang; Sanchez-Lopez, Elsa et al. (2018) New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560:198-203
Wei, Zong; Yoshihara, Eiji; He, Nanhai et al. (2018) Vitamin D Switches BAF Complexes to Protect ? Cells. Cell 173:1135-1149.e15
Caussy, Cyrielle; Hsu, Cynthia; Lo, Min-Tzu et al. (2018) Link between gut-microbiome derived metabolite and shared gene-effects with hepatic steatosis and fibrosis in NAFLD. Hepatology :

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