What we eat greatly impacts how our physiology and affects our propensity to get diseases such as obesity and diabetes. The bacteria that inhabit our intestine, our gut microbiota, greatly influence numerous physiological traits, including our nutritional intake, and also affect our response to therapeutic drugs. A major goal of biomedical research is to uncover the interplay between dietary nutrients and metabolites plus resident microbiota and the subsequent affect on our physiology. In addition, a major challenge is to dissect the mechanisms by which bacteria modulate the response to therapeutic drugs. We have developed an innovative interspecies systems biology model of the nematode C. elegans and its bacterial diet to address these questions. We have used this model to uncover bacterially derived micronutrients and metabolites that affect gene expression, development and fertility in the worm, and to identify a C. elegans metabolic regulatory network that mediates the response to bacterial nutrients. In addition, we have discovered mechanisms by which bacteria modulate the C. elegans response to several chemotherapeutic drugs. In the next project we use our demonstrated strength to investigate the effects of bacteria both broadly, in systems-level surveys and screens, and deeply with targeted mechanistic experiments. We will connect bacterial metabolism to host physiology and gene expression as well as the response to a variety of therapeutic drugs. The data obtained will provide an important stepping stone toward understanding how the microbiota can modulate human physiology in terms of nutrition and the response to xenobiotic compounds such as therapeutic drugs. This work, therefore, has long-term implications for nutrition, toxicology, as well as personalized and precision medicine.
The bacteria that inhabit our body, or our microbiota, help to digest our food, but can also modulate our response to therapeutic drug treatment. We have developed the nematode C. elegans and its bacterial diet as an interspecies model system to rapidly gain both broad systems-level and deep mechanistic insights into the connections between diet, physiology, drug response, gene expression and metabolism. We will continue to use the model system to dissect the mechanisms by which bacteria and nutrients contribute to a variety of physiological traits, gene expression and diseases.
| Hu, Queenie; D'Amora, Dayana R; MacNeil, Lesley T et al. (2018) The Caenorhabditis elegans Oxidative Stress Response Requires the NHR-49 Transcription Factor. G3 (Bethesda) 8:3857-3863 |
| Hu, Queenie; D'Amora, Dayana R; MacNeil, Lesley T et al. (2017) The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2. Genetics 206:1909-1922 |
| Yilmaz, Lutfu Safak; Walhout, Albertha J M (2014) Worms, bacteria, and micronutrients: an elegant model of our diet. Trends Genet 30:496-503 |
| Ritter, Ashlyn D; Shen, Yuan; Fuxman Bass, Juan et al. (2013) Complex expression dynamics and robustness in C. elegans insulin networks. Genome Res 23:954-65 |
| Walhout, Albertha J M (2011) Gene-centered regulatory network mapping. Methods Cell Biol 106:271-88 |
| De Masi, Federico; Grove, Christian A; Vedenko, Anastasia et al. (2011) Using a structural and logics systems approach to infer bHLH-DNA binding specificity determinants. Nucleic Acids Res 39:4553-63 |
