Modeling chronic complex diseases and treatments in Caenorhabditis elegans
Ke, Wenfan, Biology - Graduate School of Arts and Sciences, University of Virginia
O'Rourke, Eyleen, AS-Biology, University of Virginia
Chronic complex diseases (CCDs) and conditions such as cancer, type 2 diabetes, Alzheimer’s disease, heart disease, obesity, and other age-related disorders are the leading cause of death and disability in the US. It is critical to understand the molecular mechanisms underlying CCDs to develop interventions to alleviate such health, social, and economic burdens. In this dissertation, I demonstrate the approaches to study the etiology of CCDs (focusing on obesity and metabolic diseases) in the model system C. elegans and utilize C. elegans as the model to study treatments and therapies for CCDs (focusing on chemotherapy), respectively. More specifically, I described the experimental and bioinformatics pipelines to identify fat regulators in obesity in C. elegans (Chapter II), established C. elegans diet-induced obesity (DIO) model to validate the human genetic variants that potentially cause or prevent against DIO (Chapter III), and identified fat regulators in C. elegans metabolism towards the goal of developing the first predictive model of the metabolism of obesity (Chapter IV). Finally, using C. elegans-E. coli host-microbiome system, I molecularly dissected the first diet-microbiome-host-drug 4-way interaction (Chapter V). Altogether, this dissertation emphasizes the variety of the approaches to study disease mechanisms and treatment of complex diseases using the invertebrate model system C. elegans.
PHD (Doctor of Philosophy)
Chronic complex disease, Obesity, Chronic disease, Complex disease, Cancer, Diabetes, C. elegans, Human disease, Animal model, RNAi, RNAi screen, High-throughput screen, Metabolism, Genomics, Functional genomics, Causality, Metabolomics, Fat, Fat regulator, Diet-induced obesity, GWAS, Fructose, High fructose diet, Lipid droplet, Healthspan, Lifespan, Aging, Computation modeling, System biology, FUdR, Chemotherapy, Fluoropyrimidine, Serine, Thymidine, Microbiome, E. coli, Pyrimidine salvage pathway, One carbon metabolism, Folate, Toxicity, Efficacy, dTMP, Thymidine starvation, Autophagy, Autophagic cell death, AMPK, Mitochondria, DNA damage, RNA damage, LC-MS