1. Research Background

Metabolism is not just about energy production: it produces cellular building blocks and signaling molecules that are absolutely necessary for the development, reproduction, and 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 animal hosts and their microbiota. We want to understand how perturbations in host-microbe metabolic interactions contribute to disorders such as inflammatory bowel diseases or cancer. We also believe that these studies will advance our understanding of aging, a complex biological process characterized by nutritional, metabolic, and immune alterations.

2. Research questions addressed by the group:

Our current projects focus on host-microbe metabolic interactions and their impacts on health and disease.

• We study how metabolism is regulated during bacterial infection. We observed that pathogenic bacteria trigger metabolic switches in the intestine. We are currently investigating the mechanisms that underlie these responses and whether these metabolic adjustments play a protective role for the host.
• We discovered that select metabolic pathways suppress inflammatory bowel disease and sedentary behavior. We are currently dissecting these connections between metabolism, inflammatory signaling, and the gut-brain axis.
• We have evidence that hosts and bacteria cooperate to regulate gastrointestinal transit, a vital but underappreciated factor that supports nutrition in both partners. We aim to discover the bacterial activities and the host factors that regulate this complex physiological process.

3. Possible project(s):

• We want to dissect the mechanisms by which commensal bacteria regulate intestinal function, and their overall impacts on host nutrition and longevity (See Storelli et al., 2011, and Erkosar, Storelli et al., 2015, as references).
• Conversely, we wish to understand how the intestinal environment shapes the physiology of commensal bacteria (see Storelli et al., 2018 as a reference).
• We are also open to projects related to host-microbe interactions and intestinal physiology.

Ph.D. projects should be discussed directly to find the best match between the interests of the candidate and of our research group.

4. Applied Methods and model organisms:

The use of invertebrates in biomedical research reduces the reliance on mammals and supports a more humane science. The Storelli lab primarily uses the model invertebrate Drosophila melanogaster for its studies. Drosophila combine powerful genetic resources with a fast life cycle and a genetically tractable microbiota. In parallel, the mechanisms that control metabolism and host-microbe interactions are conserved between invertebrates and vertebrates. This makes Drosophila a prime model to investigate the metabolic interactions between animal hosts and their microbiome, and their overall impacts on longevity.

We combine Drosophila and bacterial genetics with transcriptomic and metabolomic approaches, as well as automated behavioral assays. We also use routine molecular biology, biochemistry, and immunohistochemistry.

The Ph.D. projects we propose are not limited to Drosophila. We aim to validate our observations in mammals, especially in organoids or cultured cells.

5. Desirable skills and qualifications:

We are looking for 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 methods can be learnt in the lab, a past experience with Drosophila, mammalian cells/intestinal organoid culture, or bacteriology is an advantage. Our group was recently established at the CECAD Research Center and currently consists of 7 members. By joining our team, you will have a close interaction 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