Semester

Spring

Date of Graduation

2020

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Biology

Committee Chair

Jennifer Gallagher

Committee Member

Jennifer Hawkins

Committee Member

Kang Mo Ku

Committee Member

Daniel Panaccione

Committee Member

Jonathan Cumming

Abstract

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry scenario with zinc, likely involving the Zrt family of zinc transporters and involving arrestin mediated endocytosis. Reactive oxygen species were generated by copper nanoparticles that induced lipid peroxidation, altering the phosphatidylcholine and phosphatidylethanolamine membrane composition, resulting in a disfigured cell surface. Following this study, I designed experiments aimed at furthering this dissertation's focus on metabolism by describing the metabolism of a novel species, Saccharomyces arboricola, thus filling a gap in knowledge in the industrial fermentation field. Low levels of endogenous amino/organic acids separated S. arboricola from the S. cerevisiae industrial strains and their interspecific hybrids showed a mosaic metabolic profile of parental strains. Overall, my dissertation research identified mechanisms of cellulosic copper nanotoxicity that included transport, metal homeostasis, reactive oxygen species, and the cellular membrane composition. Perturbations of Saccharomyces yeast by exogenous exposure to nanocopper or by interspecific hybridization had effects on the cellular metabolism.

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