Caenorhabditis elegans as a Model for Host-Microbe-Drug Interactions
Authors
Garcia Gonzalez, Aurian P.Faculty Advisor
Marian Walhout, PhDAcademic Program
MD/PhDUMass Chan Affiliations
Program in Systems BiologyDocument Type
Doctoral DissertationPublication Date
2019-04-30Keywords
C. elegansbacteria
5-FU
FUDR
tamoxifen citrate
nucleotides
fatty acids
systems biology
Organismal Biological Physiology
Systems and Integrative Physiology
Metadata
Show full item recordAbstract
The microbes that inhabit the human body, our microbiota, greatly influence our physiology and propensity for disease. For instance, the gut microbiota metabolizes compounds from our diet to provide important nutrients. Similarly, the microbiota has the potential to impact drug response; directly by metabolizing drugs, or indirectly by providing metabolites to the host. The complexity of the mammalian microbiota, and the limited throughput of such models, prohibit a systematic interrogation of specific interactions between microbes and host drug response. Here, I use C. elegans and its bacterial diet as a suitable model with the scalability and genetic tractability to address these questions. In Chapter II, I describe host-bacteria-drug interactions involving the anti-pyrimidine drugs 5-FU and FUDR. In brief, we identified two main mechanisms by which bacteria affect the C. elegans response to anti-pyrimidines: (1) metabolic conversion into FUMP by uridine phospho-ribosyltransferase (upp) and (2) dietary supplementation of uracil. Chapter III will focus on a selective estrogen-receptor modulator, TAM, with no clear target in bacteria or C. elegans. I will describe my work characterizing a bacteria-dependent response to TAM involving fatty acid metabolism. Lastly, the Appendix will summarize my efforts to expand the sample space of tested host-microbe-drug interactions.DOI
10.13028/f7aw-3240Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31243Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/f7aw-3240