Date of Award
Doctor of Philosophy
Gary S. Sayler
Alison Buchan, Erik Zinser, Qiang He, Jerome Baudry
The impact of endocrine disruptive chemicals to human and wild life health has raised serious public health concerns through the past decades. To address this concern, much research was involved to develop tools for screening and assessing the hormonal potential of these compounds. Yeast bioluminescent bioreporter assay was one of the tools developed as the result of these past research endeavors. In this dissertation, a yeast bioluminescent bioreporter assay system was evaluated for the screening of endocrine disruptors from both experimental and computational perspectives. The yeast bioluminescent bioreporters were first standardized and applied in the comparative study of traditional activated sludge and membrane bioreactor wastewater treatment facilities for their performance in endocrine disruptor removal. Then the interaction between endocrine disruptors and their target, human estrogen receptor (hER), was studied by both computational modelling and experimental approaches. Specifically, the effects of naturally occurring mutations on hER were investigated for their interaction with 29 estrogenic endocrine disruptors through molecular dynamics simulation and virtual docking. To verify the predicted results from computational modelling, new yeast bioluminescent reporters harboring the mutated hER were constructed to evaluate the hER-mediated transactivation triggered by 12 selected endocrine disruptors. hER mutations caused various degree and pattern of changes in the response to the 12 tested endocrine disruptors in the yeast bioassay. The potential mechanism for the altered ER mutant response and their possible health related impacts were discussed.
Wang, Jun, "Computational Perspective for Developing Bioluminescent Yeast Estrogen Screens for Environmental Toxicology. " PhD diss., University of Tennessee, 2016.