Metabolism lies at the heart of most if not all biological processes to generate biomass during development and in wound healing, to generate energy to support cellular and organismal processes, and to detoxify exogenous and endogenous toxic compounds. We will study metabolic perturbations using gene mutants and metabolite supplementations on physiological and molecular phenotypes in the nematode C. elegans and examine the effect of bacterial diet on these phenotypes. We will focus on perturbations associated with inborn errors of metabolism (IEMs), which are human metabolic disorders that are caused by mutations (usually recessive) in metabolic enzymes and transporters. This work will shed light on the basic mechanisms of how an animal responds to different metabolic perturbations and how environmental factors such as diet and microbiota modulate them. These studies may further provide hypotheses relevant for studies in larger eukaryotes, including humans.