ABSTRACT: CHEMISTRY AND ANALYICAL CORE The Chemistry and Analytical Core (CAC) is a critical research support core for the UNC-SRP, providing expertise and analytical capabilities to measure toxic substances with prioritization of inorganic arsenic (iAs) and co-occurring contaminants and characterize their effects on metabolic dysfunction/diabetes. The CAC offers analytical expertise and services, access to state-of-the-art instrumentation for metals measurements, microbiome and biomarker/metabolomics analysis, and training in cutting-edge research methodologies. The CAC provides Projects 1-5 with the tools and expertise needed to generate critical data sets that will help to identify novel strategies to reduce iAs exposure and to prevent iAs-induced metabolic dysfunction. The CAC staff accomplishes tasks through utilization of a versatile Agilent inductively coupled plasma mass spectrometry (ICP-MS) and a hydride generation-cryotrapping-atomic absorption spectrometer (HG-CT-AAS) for total element and speciation analysis, highly sensitive AB Sciex and Thermo TSQ triple quadrupole MS for biomarker quantitation, and high resolution Thermo QE HF Orbitrap MS for metabolomics profiling and metabolite identification. In addition, the CAC has established expertise in microbiome analysis via 16S rRNA gene sequencing and shotgun metagenomics. The overall objective of the Chemistry and Analytical Core is to provide the UNC-SRP Projects with analytical infrastructure, instrumentation, analytical service and related training. Three specific aims will be pursued, including: Aim 1. Develop and implement analytical methodologies, with a focus on separation, detection and quantitation of metals and their metabolites/species; Aim 2. Examine toxicant-induced gut microbiome perturbation and metabolic disruption through metagenomics and metabolomics; and Aim 3. Provide consultation to Biomedical and Environmental Science Projects and a supportive environment for graduate student and postdoctoral training on state-of-the-art analytical equipment. The CAC supports the overall theme of the UNC-SRP: “Identifying novel methods to reduce iAs exposure and elucidating mechanisms underlying iAs-induced metabolic dysfunction with a vision for disease prevention.” !The CAC activities promote interaction among all Projects and Cores through expertise in metals analyses, microbiome and biomarker/metabolomics analysis that is critical in guiding the Projects’ research strategies. With every component in place, including state-of-the-art equipment, rigorous QA/QC plans, highly experienced personnel and a strong leadership team and institutional support, the CAC will play a key role in forging links among the Center researchers. !

NARRATIVE: CHEMISTRY AND ANALYTICAL CORE The overarching goal of Chemistry and Analytical Core (CAC) is to develop and apply ultra-sensitive and specific analytical methods to measure metals (iAs, its species and other Superfund contaminants) in environmental and biological samples and characterize toxicant-induced adverse health effects via microbiome and biomarker/metabolomics approaches. These data provide critical research support for all UNC-SRP projects and promote the integration of the UNC-SRP to better understand and protect the public from adverse health effects related to Superfund chemicals. ! !