Descrizione del progetto
Un nuovo studio cerca di svelare i meccanismi di modellazione dei tessuti
Il progetto ACE-OF-SPACE, finanziato dall’UE, affronterà un interrogativo secolare in materia di biologia dello sviluppo. Come sono modellati i tessuti nel tempo e nello spazio, e in che modo cellule identiche si differenziano per formare lo schema corporeo maturo? Tali processi di formazione degli schemi sono coordinati da determinate molecole di segnalazione. Tuttavia, non è ancora chiaro con quale precisione vengano trasmessi questi segnali e in che modo le cellule interagiscano tra loro per interpretare queste informazioni. Inoltre, è stato difficile visualizzare direttamente in che modo le molecole di segnalazione modellano gli embrioni e definire i requisiti minimi per la modellazione auto-organizzata. Il progetto lavorerà su embrioni di pesci zebra, cellule staminali embrionali di topi e colonie batteriche. I risultati produrranno approfondimenti entusiasmanti nella comunicazione tra le cellule così come nell’ingegneria tissutale.
Obiettivo
A central problem in developmental biology is to understand how tissues are patterned in time and space - how do identical cells differentiate to form the adult body plan? Patterns often arise from prior asymmetries in developing embryos, but there is also increasing evidence for self-organizing mechanisms that can break the symmetry of an initially homogeneous cell population. These patterning processes are mediated by a small number of signaling molecules, including the TGF-β superfamily members BMP and Nodal. While we have begun to analyze how biophysical properties such as signal diffusion and stability contribute to axis formation and tissue allocation during vertebrate embryogenesis, three key questions remain. First, how does signaling cross-talk control robust patterning in developing tissues? Opposing sources of Nodal and BMP are sufficient to produce secondary zebrafish axes, but it is unclear how the signals interact to orchestrate this mysterious process. Second, how do signaling systems self-organize to pattern tissues in the absence of prior asymmetries? Recent evidence indicates that axis formation in mammalian embryos is independent of maternal and extra-embryonic tissues, but the mechanism underlying this self-organized patterning is unknown. Third, what are the minimal requirements to engineer synthetic self-organizing systems? Our theoretical analyses suggest that self-organizing reaction-diffusion systems are more common and robust than previously thought, but this has so far not been experimentally demonstrated. We will address these questions in zebrafish embryos, mouse embryonic stem cells, and bacterial colonies using a combination of quantitative imaging, optogenetics, mathematical modeling, and synthetic biology. In addition to providing insights into signaling and development, this high-risk/high-gain approach opens exciting new strategies for tissue engineering by providing asymmetric or temporally regulated signaling in organ precursors.
Campo scientifico
- natural sciencesbiological sciencessynthetic biology
- natural sciencesbiological sciencesdevelopmental biology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineembryology
- natural sciencesmathematicsapplied mathematicsmathematical model
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
78464 Konstanz
Germania