Organ Homeostasis & Physiology Lab
Multicellular organisms have evolved organs and tissues with highly specialized tasks. The function of each organ is modified by local clues and systemic signals derived from other organs to ensure a coordinated response accommodating the physiological needs of the organism. The intestine, which represents one of the largest interfaces with the external environment, plays a key role in relaying environmental inputs to other organs to produce systemic responses. In turn, the gut is subject to multiple regulatory inputs from the brain, muscles, liver and adipose tissues. At steady-state turnover rates, the human intestine undergoes complete self-renewal every 4-5 days, a process which is highly accelerated in response to damage of the gut epithelium. This capacity for self-renewal relies on the proliferative activity of the intestinal stem cells (ISCs), which is tightly controlled by multiple local and systemic signals released from neighboring cell populations (the ISC niche) and non-gastrointestinal organs. Despite the physiological divergence between insects and mammals, studies have shown that drosophila represents a model that is well suited for studying stem cell physiology during ageing, stress, and infection. Our team is interested in identifying the intra- and inter-organ couplings contributing to gut homeostasis and disease.
- Project 1
- Project 2 The team is also interested in role of Tumor Necrosis Factor (TNF) signalling in intestinal homeostasis and disease. Whereas, excess TNF-alpha signalling induces apoptosis and contributes to GI pathologies in humans, it is also a critical protective factor promoting GI homeostasis following injury. Flies represents a convenient model for studying the complex role of TNF/TNFR signalling in GI disease in vivo due to lack of redundancy in downstream effectors. We previously showed that the fly TNFR, Grindelwald, is activated by the unique fly TNF ligand, but also in a ligand-independent manner in response to loss of cell polarity. We are currently investigating the contribution of ligand-independent TNFR signalling to gut homeostasis and disease. This could prove useful for the future design of anti-TNF therapeutics, since the current anti-TNF therapeutic regimes aiming at preventing the binding of TNF-alpha to its receptors, have proved inefficient in a significant number of patients with inflammatory bowel disease (IBD).
Novo Nordisk Foundation Young Investigator Award 2020-2026
Inter-Organ Growth Coordination Is Mediated by the Xrp1-Dilp8 Axis in Drosophila.
Boulan, L.; Andersen, D.S.; Colombani, J.; Boone, E.; Léopold, P.
Developmental Cell, 2019 Apr 16. pii: S1534-5807(19)30227-8. doi: 10.1016/j.devcel.2019.03.016. [Epub ahead of print].
A Drosophila Tumor Suppressor Gene Prevents Tonic TNF Signaling through Receptor N-Glycosylation.
de Vreede, G.; Morrison, H.A.; Houser, A.M; Boileau, R.M.; Andersen, D.S.; Colombani, J.; Bilder, D.
Developmental Cell, Vol. 45, No. 5, 04.06.2018, p. 595-605.
The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8 expression.
Boone, E.; Colombani, J.; Andersen, D.S.; Léopold, P.
Nature Communications, Vol. 7, 22.11.2016, p. 13505.
The Drosophila TNF receptor Grindelwald couples loss of cell polarity and neoplastic growth.
Andersen, D.S.; Colombani, J.; Palmerini, V.; Chakrabandhu, K.; Boone, E.; Röthlisberger, M.; Togweiler, J.; Basler, K.; Mapelli, M.; Hueber, A.O.; Léopold, P.
Nature, Vol. 522, No. 7557, 25.06.2015, p. 482-6.
Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability.
Colombani, J.; Andersen, D.S.; Boulan, L.; Boone, E.; Romero, N.; Virolle, V.; Texada, M.; Léopold, P.
Current biology, Vol. 25, No. 20, 19.10.2015, p. 2723-9.
Coordination of organ growth : principles and outstanding questions from the world of insects.
Andersen, D.S.; Colombani, J.; Léopold, P.
Trends in Cell Biology, Vol. 23, No. 7, 07.2013, p. 336-44.
Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing.
Colombani, J.; Andersen, D.S.; Léopold, P.
Science, Vol. 336, No. 6081, 04.05.2012, p. 582-5.