Research Area: Stress Signaling and Metabolism
1. Research Background
The Storelli lab is interested in a basic, but fundamental question: how do living organisms maintain homeostasis despite constant internal and environmental perturbations? Among the mechanisms involved in these adaptations, we are particularly interested in the crosstalk between stress signaling and metabolic pathways. Understanding how metabolism is adjusted to maintain tissue physiology and systemic homeostasis during stress will not only expand our knowledge of animal physiology – it could deliver key insights into the deleterious effects of aging, a complex biological process characterized by both chronic activation of stress signaling and metabolic dysfunction.
2. Research questions addressed by the group:
The Storelli lab uses the model invertebrate Drosophila melanogaster to investigate the connections between stress signaling pathways and cellular metabolism. Drosophila are relevant for these studies: they have organs analog to all of the key metabolic tissues found in more complex organisms, and the basic mechanisms of metabolic control and stress signaling are conserved between invertebrates and vertebrates. The use of Drosophila therefore helps reducing the reliance on rodents to study these pathways, in compliance with the principle of the 3Rs (Replacement, Reduction and Refinement). In addition, Drosophila combine powerful genetic resources with a fast life cycle. These characteristics allow both large-scale or very focused approaches, at the level of tissues or even cell types, making Drosophila a prime model to investigate the complex etiology of aging-related disorders.
The Storelli lab currently follows 3 main research aims:
- We want to understand the role of specific metabolic pathways in supporting development and longevity. Metabolism is not just about energy production - it can produce signaling agents or cellular building blocks that are absolutely necessary for the growth of the organism or the maintenance of systemic homeostasis. We want to understand how animals adjust their metabolism over the course of their lives, to meet the needs of each stage of their life cycle (Please see (Storelli et al. Dev cell. 2019) as an example).
- We wish to characterize how stress signaling and metabolic pathways regulate each-other. Along these lines, we currently investigate the connections between select pathways of lipid metabolism and inflammatory signaling. We also investigate how nutritionally, chemically, or genetically-induced stress impacts metabolism in select tissues, and the roles for these tissue-specific metabolic responses in supporting survival.
- We wish to draw the limits of these homeostatic roles for stress signaling and metabolism. For example, we want to determine if the chronic activation of inflammatory signaling seen during aging or in inflammatory bowel disease favors the onset of secondary disorders by primarily perturbing metabolism.
3. Possible project:
We have several projects that fit with a Ph.D. training, all of which relate to the 3 research aims outlined above. Please note that potential Ph.D. projects are not restricted to Drosophila: we are interested in translating some of our observations in the mouse, in particular through mammalian organoid or cell culture.
The Ph.D. projects should be discussed directly, to find the best match between the candidate and our research group.
4. Applied Methods and model organisms:
The Storelli lab combines Drosophila genetics with transcriptomic and metabolomic approaches, as well as automated behavioral assays to investigate the roles for cellular metabolism in supporting systemic homeostasis. We also use routine molecular biology, biochemistry and immunohistochemistry technics, as wells as assays to score select metabolites.
5. Desirable skills and qualifications:
We seek a curious, enthusiastic, and creative Ph.D. student who has a strong interest in stress signaling, metabolism or physiology. While all of the above-mentioned methods can be learnt in the lab, a past experience with Drosophila or intestinal organoid culture is a strong advantage.
Our group has recently been established at the CECAD Research Center and is currently composed of 4 members. By joining our team, you will have close interactions with your lab mates 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 plantarum promotes 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