1. Research Background
Metabolism is not just about energy production - it produces cellular building blocks and signaling agents that are absolutely necessary for the development, reproduction, and the maintenance of homeostasis in all organisms (See Storelli et al., 2019 as a reference). The overall metabolic capabilities of metazoans are encoded in their genome, and in their microbiome (the set of genes carried by symbiotic microorganisms). Our group is interested in the mechanisms that regulate metabolism, in both animal hosts and their microbiota. Our overarching goal is to understand how deregulations in metabolism can lead to the development of certain pathologies, such as inflammatory bowel diseases or cancer. We also think that these studies will broaden our understanding of aging, a complex biological process characterized by metabolic dysregulation, nutritional deficiencies, and chronic activation of stress signaling.
2. Research questions addressed by the group:
Our current projects use the invertebrate model Drosophila melanogaster and mammalian cell culture, and are centered around the roles for metabolism in intestinal health and disease.
- We investigate how cellular metabolism is adjusted during intestinal stress, to support tissue function and epithelial homeostasis. In particular, we are interested in the metabolic switches that occur in the intestine, in response to epithelial insults.
- We discovered that select metabolic pathways suppress inflammatory bowel disease and sedentary behavior in Drosophila. We currently investigate these connections between cellular metabolism, inflammatory signaling, and the gut/brain axis.
3. Possible project:
The Ph.D. projects we propose are centered around host/microbiota metabolic interactions:
- We wish to dissect the mechanisms by which commensal bacteria regulate intestinal function, and their overall impacts on host nutrition, longevity, and aging (See Storelli et al., 2011, and Erkosar, Storelli et al., 2015, as references).
- Conversely, we want to investigate how intestinal metabolism shapes the physiology of commensal bacteria (see Storelli et al., 2018 as a reference).
- We are also open to suggestions, as long as the projects are linked to intestinal metabolism and/or physiology.
The Ph.D. projects should be discussed directly in more details, to find the best match between the interests of the candidate and our research group. Please note that potential Ph.D. projects are not restricted to Drosophila: we are interested in translating some of our observations in mammals, especially through mammalian organoid or cell culture.
4. Applied Methods and model organisms:
The Storelli lab uses mammalian cell culture and the model invertebrate Drosophila to study metabolism. Drosophila combine powerful genetic resources with a fast life cycle and a genetically-tractable microbiota, while the basic mechanisms of metabolic control are conserved between invertebrates and vertebrates. These characteristics make of Drosophila a prime model to investigate the complex metabolic interactions that occur between animal hosts and their symbiotic microbes.
We combine Drosophila genetics with bacteriology, transcriptomic, and metabolomic approaches, as well as automated behavioral assays. We also use routine molecular biology, biochemistry, and immunohistochemistry technics, as well as metabolite assays for our studies.
5. Desirable skills and qualifications:
We seek a curious, enthusiastic, and creative Ph.D. student who has a strong interest in stress signaling, metabolism, physiology, or bacteriology. While all of the above-mentioned methods can be learnt in the lab, a past experience with Drosophila, mammalian cells/intestinal organoid culture, or bacteriology is an advantage. Our group has recently been established at the CECAD Research Center and is currently composed of 6 members. By joining our team, you will have close interactions with your colleagues and your supervisor. You must be fluent in English, as this is the working language in the lab.
6. References and key publications:
- Storelli, G.*, Nam, H.J., Simcox, J., Villanueva, C.J., and Thummel, C.S.* (2019). Drosophila HNF4 directs a switch in lipid metabolism that supports the transition to adulthood. Dev Cell. 48(2):200-214.e6. (Featured in a preview article in Dev Cell. 48(2):133-134.)*Co-corresponding author
- Storelli, G.*, Strigini, M., Grenier, T., Bozonnet, L., Schwarzer, M., Daniel, C., Matos, R., and Leulier, F*. (2018). Drosophila perpetuates nutritional mutualism by promoting the fitness of its intestinal symbiont Lactobacillus plantarum. Cell Metab. 27(2):362-377.e8. (Featured in a preview in Cell Metab. 27(2):267-268.)*Co-corresponding author
- Schwarzer, M., Makki, K., Storelli, G., Machuca-Gayet, I., Srutkova, D., Hermanova, P., Martino, M.E., Balmand, S., Hudcovic, T., Heddi, A., et al. (2016). Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science. 351(6275):854-857.
- Erkosar, B.*, Storelli, G. *, Mitchell, M., Bozonnet, L., Bozonnet, N., and Leulier, F. (2015). Pathogen virulence impedes mutualist-mediated enhancement of host juvenile growth via inhibition of protein digestion. Cell Host Microbe. 18(4):445-55. (Featured in a preview article in Cell Host Microbe. 18(4):388-390.)*Co-first author
- Storelli, G.*, Defaye, A.*, Erkosar, B., Hols, P., Royet, J., and Leulier, F. (2011). Lactobacillus plantarumpromotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab. 14(3):403-414. (Featured in a preview article in Cell Metab. 18(4):283-284.) *Co-first author