Descripción del proyecto
Ha nacido una estrella: las estrellas de actina y su papel en la homeostasis del epitelio intestinal
La proliferación y diferenciación de las células madre son procesos esenciales durante el desarrollo y a lo largo de toda la vida. Las células madre sirven a la homeostasis de los tejidos y a la renovación, reparación y regeneración continuas de los tejidos y órganos. Los mecanismos subyacentes a la homeostasis tisular no se conocen bien. El equipo del proyecto ActinStar, que cuenta con el apoyo de las Acciones Marie Skłodowska-Curie, investigará el papel potencial de un ensamblaje de actina multicelular en forma de estrella descubierto recientemente, denominado «estrella de actina», en la diferenciación de células madre y la homeostasis tisular en la salud y la enfermedad. El trabajo del proyecto se centrará en la homeostasis intestinal y el epitelio, un tejido que recubre todas las superficies internas y externas del cuerpo y que se regenera constantemente.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinador
75794 Paris
Francia