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Destabilization of the Epithelial Tissue Architecture by Competition with e cadh...

Destabilization of the Epithelial Tissue Architecture by Competition with e cadherin Homo dimer formation small molecule induced disruption of the epithelium integrity and functions Cadherin expression on the surface of cells is critical for cell-cell adhesion and, consequently, for the development and the integrity of solid tissues. In mammals, impaired cadherin mediated adhesion has been implicated in all s... ver más

31/10/2014

IIT

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2014-10-31 No tenemos la información de la convocatoria

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

IIT

0.00€ | Lider

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Líder del proyecto

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cadherin expression on the surface of cells is critical for cell-cell adhesion and, consequently, for the development and the integrity of solid tissues. In mammals, impaired cadherin mediated adhesion has been implicated in all steps of tumor progression. E-cadherin, a prominent member of the cadherin family, is expressed on the surface of epithelial cells in the digestive tract, in the lungs as well as in the testis and other organs and is therefore responsible for the integrity of the mucosal tissues that protect a vast surface of the inner body. Cell adhesion mediated by E-cadherin and other type I cadherins involves homophilic trans interactions that are brought about by a strand exchange mechanism involving the N-terminal extracellular domain. The epithelial tissue constitutes the body’s first line of defense and, as such, is exposed to a large number of small, potentially toxic molecules from the environment whose chemical and structural features are reminiscent of the tryptophan residue (Trp2) used by E-cadherin in its dimerization mechanism. These molecules can mimic the Trp2 function in E-cadherin by inserting into the hydrophobic acceptor pocket of E-cadherin and by occuping the site of Trp2 docking, thus potentially interfering with the E-cadherin mechanism of self-adhesion. We hypothesize that such events can disrupt the integrity of the epithelial tissue, ultimately causing tissue remodeling and the loss of the epithelium’s protective properties. The main aim of this project is to use X-ray crystallographic analysis to determine whether a number of known environmental pollutants that are present in the atmosphere as well as in foods or other media to which the population is commonly exposed can bind into or in the vicinity of the E-cadherin hydrophobic pocket or cause structural changes that prevent E-cadherin dimerization, thus causing disruption in the integrity of the body’s first line of defense.

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