Role of microvilli and adhesion receptors in the vesicular intracellular trafficking of hepatic organoids

Línea de investigación

Biología Celular de la Inflamación.

Descripción

Inflammation constitutes the initial response to infection, stress, or tissue damage. Pathological inflammation leads to chronic pathologies such as arteriosclerosis, multiple sclerosis, or hepatitis, as well as to acute, systemic, and lethal diseases such as septicemia. Inflammatory responses are orchestrated by the secretion of cytokines in the vicinity of the inflammatory focus, which produce, among other effects, the alteration of endothelial and epithelial barrier function in tissue parenchyma, thus facilitating the passage of soluble mediators and immune cells into the inflamed region. Our main objective is to investigate the effect of these inflammatory mediators on cellular barrier function and, reciprocally, to study how these barriers regulate the inflammatory response.

Part of our research interest is focused on hepatic epithelial cells, in which we have demonstrated the reciprocal relationship between the inflammatory response and their apicobasal polarity, mechanistically supported by the polarization and signaling capacity of the ICAM-1 adhesion receptor (Reglero-Real et al., Cell Rep, 2014, Marcos-Ramiro, J Cell Biol, 2016; Cacho-Navas et al., CMLS, 2022). To demonstrate that this new role for ICAM-1 is independent of its function mediating lymphocyte adhesion, we have developed and cultured hepatic organoids in 3D from liver bipotent precursors (Cacho-Navas et al., eLife 2024, Blazquez-Garcia et al. J Proteome Res 2024).

To investigate further the role of ICAM-1 on apicobasal polarity, our laboratory has identified new components of the ICAM-1 interactome, which consist of proteins involved in intracellular trafficking and the formation and maintenance of microvilli. Within this context, to investigate whether ICAM-1 and surface microvilli regulate vesicular exocytosis in hepatic epithelia, the student will get familiar with the culture of epithelial and endothelial cell barriers and liver organoids, their stimulation with inflammatory cytokines and cellular analyses by high-resolution confocal microscopy in polarized hepatic cells and organoids. She/he will get also familiar with CRISP-CAS9 and siRNA technology to edit and silence genes, respectively, as well as with modern biochemical strategies to investigate protein-protein interactions. The Cell Biology of Inflammation lab is a young research group, passionate for science, which make use of state-of-the-art technology to respond essential questions in the field of physio-pathological inflammation.

Contacto

Jaime Millán Martínez.

Correo electrónico: jmillan@cbm.csic.es.

Centro de Biología Molecular Severo Ochoa (CBM).

Número de plazas ofertadas: 1.