PROJECT 1 This project will develop and evaluate a comprehensive and integrated suite of analytical, computational, and bioassay based approaches for assessing overall reductions in toxicity resulting from bioremediation of Superfund (SF) sites. These tools will then be applied to optimize biodegradation of two contaminant mixtures, triazine herbicides and polycyclic aromatic hydrocarbons representative of environmental exposures faced by our community partners the Yurok Tribe, through systematic investigation of carbon sources, electron acceptors, and reactor detention times. Although both of these contaminant mixtures are known to biodegrade, transformation products (TPs) accumulate and are widely found in groundwater (triazines) and/or have increased toxicity compared to parent compounds (PAHs). Bioreactor performance will be characterized by measuring shifts in microbial community composition, bioassay activity, and both target and nontarget chemical concentrations measured with GC and LC high resolution mass spectrometry (HRMS). This combination of measurements will provide unique insights into interactions among contaminant transformations, microbial populations and overall reductions in human and ecosystem risks. Novel enzyme engineering approaches will be used to identify rate limiting steps in triazine mineralization and to isolate or design improved enzymes to carry out these steps. Microorganisms with improved ability to degrade triazines will be prepared and tested in the bioreactors to assess ability to remove target compounds and to reduce overall bioactivity compared to standard enrichment approaches. Our central hypothesis is that chemical hazard reduction during SF site remediation can be best characterized through broad consideration of both contaminant destruction and byproduct formation. We further hypothesize that a minimum suite of high- throughput assays can be defined to effectively capture the overall risk reduction during remediation and that this suite of assays can guide optimization of bioreactor design and operation. This project will support a paradigm shift in the SRP away from reducing concentrations of specific constituents and toward the overall reduction of deleterious biological effects. The project is strongly integrated with the overall program, drawing on HRMS, metabolomics, and statistical expertise in the Analytical Core, the full range of bioassays available in the Bioanalytical Core, immunoassays from Project 3 especially for triazines and TPs, as well as integrative bioassays for ER and oxidative stress being developed by Projects 4 and 5. The bioassay suite developed here will be used to analyze environmental samples collected through the Community Engagement Core and the overall workflow will be transferred to a broader user community with the assistance of the Research Translation Core.

Public Health Relevance

PROJECT 1 Bioremediation is often limited for superfund site remediation by slow transformation rates and/or buildup of transformation products, possibly having higher toxicity than the parent compounds. This project will demonstrate significant improvements in bioremediation via a multi-prong effort involving non-target chemical analysis, a comprehensive suite of bioassays and enzyme engineering. It will thus lead to reductions in human exposure to bioactive compounds and to more rapid and effective site cleanups, making it of direct interest to Superfund Research Program stakeholders, especially communities like the Yurok Tribe that face unknown contamination scenarios.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
3P42ES004699-30S1
Application #
9707159
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Henry, Heather F
Project Start
Project End
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
30
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Mao, Yuxin; Pan, Yang; Li, Xuan et al. (2018) High-precision digital droplet pipetting enabled by a plug-and-play microfluidic pipetting chip. Lab Chip 18:2720-2729
Burmistrov, Vladimir; Morisseau, Christophe; Harris, Todd R et al. (2018) Effects of adamantane alterations on soluble epoxide hydrolase inhibition potency, physical properties and metabolic stability. Bioorg Chem 76:510-527
Stamou, Marianna; Grodzki, Ana Cristina; van Oostrum, Marc et al. (2018) Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex. J Neuroinflammation 15:7
Huo, Jingqian; Li, Zhenfeng; Wan, Debin et al. (2018) Development of a Highly Sensitive Direct Competitive Fluorescence Enzyme Immunoassay Based on a Nanobody-Alkaline Phosphatase Fusion Protein for Detection of 3-Phenoxybenzoic Acid in Urine. J Agric Food Chem 66:11284-11290
Zamuruyev, Konstantin O; Borras, Eva; Pettit, Dayna R et al. (2018) Effect of temperature control on the metabolite content in exhaled breath condensate. Anal Chim Acta 1006:49-60
Zamuruyev, Konstantin O; Schmidt, Alexander J; Borras, Eva et al. (2018) Power-efficient self-cleaning hydrophilic condenser surface for portable exhaled breath condensate (EBC) metabolomic sampling. J Breath Res 12:036020
Burmistrov, Vladimir; Morisseau, Christophe; Pitushkin, Dmitry et al. (2018) Adamantyl thioureas as soluble epoxide hydrolase inhibitors. Bioorg Med Chem Lett 28:2302-2313
Philippat, Claire; Barkoski, Jacqueline; Tancredi, Daniel J et al. (2018) Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort. Int J Hyg Environ Health 221:548-555
Tu, Ranran; Armstrong, Jillian; Lee, Kin Sing Stephen et al. (2018) Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia. Sci Rep 8:5279
Wang, Weicang; Yang, Jun; Zhang, Jianan et al. (2018) Lipidomic profiling reveals soluble epoxide hydrolase as a therapeutic target of obesity-induced colonic inflammation. Proc Natl Acad Sci U S A 115:5283-5288

Showing the most recent 10 out of 1149 publications