Soils and waters with high levels of toxic heavy metals such as cadmium, arsenic, lead and mercury are detrimental to human and environmental health. These 4 metal(loid)s are among the Superfund's top 7 priority hazardous substances. Recent research and applications indicate that uptake of heavy metals into plants via the root system and accumulation of heavy metals in plant shoots could provide a cost effective approach for toxic metal removal and remediation of heavy metal-laden soils and waters. However many genes, mechanisms and pathways that function in heavy metal over-accumulation in plants remain to be identified and characterized. Phytochelatins are major heavy metal and metalloid chelating and detoxifying thiolate peptides in plants. In recent research we have made advances at understanding mechanisms that contribute to heavy metal detoxification and transport in plants, including isolation of phytochelatin synthase genes, characterization of mechanisms for root to shoot transfer of cadmium, isolation of heavy metal accumulation Arabidopsis mutants, development of a novel microarray-based rapid mutant cloning approach and microarray-based identification of putative transporter genes that may contribute to heavy metal transport. The investigators will test the hypotheses that, phytochelatins affect long distance root to leaf vascular transport of toxic metals;characterization of new toxic metal accumulation mutants will lead to identification of rate-limiting steps that function in plant heavy metal accumulation;and heavy metal sensing and signal transduction mechanisms in plants are important for plant heavy metal resistance and accumulation. To test these hypotheses, the proposed project will, in Specific Aims 1 and 2, characterize novel physiological and molecular mechanisms of root to shoot transport of heavy metals and phytochelatins using physiological, genomic, biochemical and membrane transport analyses. By pursuing a new high-throughput screening approach in collaborative research, the investigators have identified Arabidopsis mutants that affect the accumulation of toxic metals in leaves.
In Specific Aim 3, a newly developed genomic microarray-based rapid mutant mapping and cloning approach will be used to isolate selected heavy metal accumulation mutant genes and characterize the underlying mechanisms.
Specific Aim 4 will be to characterize heavy metal biosensing and transduction mechanisms in plants using a luciferase reporter screen. Trials with contaminated soils from Superfund sites will be pursued in collaboration with Edenspace Corp (in Specific Aim 5), to assess the feasibility of monitoring bioavailable heavy metals and of hyperaccumulating heavy metals and metalloids into plant roots and shoots using transgenic and mutant plants generated in this research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010337-10
Application #
7799238
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
10
Fiscal Year
2009
Total Cost
$238,065
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Hsu, Po-Kai; Takahashi, Yohei; Munemasa, Shintaro et al. (2018) Abscisic acid-independent stomatal CO2 signal transduction pathway and convergence of CO2 and ABA signaling downstream of OST1 kinase. Proc Natl Acad Sci U S A 115:E9971-E9980
Dhar, Debanjan; Antonucci, Laura; Nakagawa, Hayato et al. (2018) Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling. Cancer Cell 33:1061-1077.e6
Febbraio, Mark A; Reibe, Saskia; Shalapour, Shabnam et al. (2018) Preclinical Models for Studying NASH-Driven HCC: How Useful Are They? Cell Metab :
Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H (2018) Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans. Drug Metab Pharmacokinet 33:9-16
Hartmann, Phillipp; Hochrath, Katrin; Horvath, Angela et al. (2018) Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice. Hepatology 67:2150-2166
Ganguly, Abantika; Guo, Lan; Sun, Lingling et al. (2018) Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks. PLoS Genet 14:e1007595
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:397-411
Chen, Shujuan; Tukey, Robert H (2018) Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice. Drug Metab Dispos 46:1745-1755
Desai, Archita P; Mohan, Prashanthinie; Roubal, Anne M et al. (2018) Geographic Variability in Liver Disease-Related Mortality Rates in the United States. Am J Med 131:728-734
Ajmera, Veeral; Park, Charlie C; Caussy, Cyrielle et al. (2018) Magnetic Resonance Imaging Proton Density Fat Fraction Associates With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 155:307-310.e2

Showing the most recent 10 out of 404 publications