Descrizione del progetto
Le stelle di actina e il loro ruolo nell’omeostasi dell’epitelio intestinale
La proliferazione e la differenziazione delle cellule staminali sono processi essenziali durante lo sviluppo e nel corso della vita. Il secondo di questi è alla base del continuo rinnovamento, riparazione e rigenerazione di tessuti e organi, nonché dell’omeostasi tissutale, il cui funzionamento si basa su meccanismi non ancora ben compresi. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto ActinStar studierà il potenziale ruolo svolto nella differenziazione delle cellule staminali e nell’omeostasi dei tessuti in condizioni di salute e malattia da un assemblaggio multicellulare di actine, a forma di stella, recentemente scoperto che è stato chiamato stella di actina. Il lavoro svolto nell’ambito del progetto si concentrerà sull’omeostasi intestinale e sull’epitelio, un tessuto che ricopre tutte le superfici interne ed esterne del corpo e si rigenera in modo costante.
Obiettivo
Faithful epithelial morphogenesis is crucial during development and tissue homeostasis. The dynamic intestinal epithelium is an appropriate model to study this field of research. Constant regeneration of epithelium is one of the main characteristics of intestinal homeostasis mediated by finely controlled balance between intestinal stem cell proliferation and differentiation. Therefore, it is instrumental to study mechanisms controlling intestinal organization to understand tissue homeostasis and function.
Actin cytoskeleton plays an important role in regulating epithelial morphogenesis. Recently, by using 2D and 3D intestinal organoids, the host lab has discovered a new unique multicellular star-shaped actin assembly, termed “actin stars” (AcSs) located in the basal domain of differentiated epithelium. This network is characterized by 6-branched star-shaped actin clusters covering the entire basal surface, with AcS node at the centroid of the cell and each branch of the star orthoradially connects the plasma membrane, and directly mirrors a corresponding branch from a neighbouring cell. They confirmed such actin structures in vivo in mouse small intestine. The AcSs may represent a large-scale inter-connecting meshwork in the differentiated epithelial domain.
Considering the novelty of these results, we would like to investigate the interplay between large-scale AcS networks and tissue morphogenesis. Here we aim to dissect the organization of AcS network, determine the processes leading to their formation, and understand the importance of AcSs for individual cells as well as epithelial assemblies. For that we will carry out a multi-disciplinary approach, combining the use of high-resolution imaging, optogenetics, genomics coupled to physical modelling.
We anticipate that our results will have a significant impact in understanding the role of AcSs in epithelial differentiation, tissue homeostasis in physiological and pathological conditions.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
75794 Paris
Francia