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Angio-NYT

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Investigating the crosstalk between Notch and YAP TAZ in sprouting angiogenesis

Our limited understanding of angiogenesis, the process leading to the formation of new blood vessels from pre-existing ones, hinders the design of new treatments for associated diseases such as cancer, ischemia, and diabetic retin... ver más

31/08/2022

TU/e

170K€

Presupuesto del proyecto: 170K€

Líder del proyecto

TECHNISCHE UNIVERSITEIT EINDHOVEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Ver 3 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-08-31

MSCA-IF-2018: Individual Fellowships

I+D

Cerrada hace 6 años

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Información adicional privada

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

3 Participantes

TU/e

170.42K€ | Lider

THE TRUSTEES OF BOSTON UNIVE...

82.63K€ | Participante

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Duración del proyecto: 37 meses Fecha Inicio: 2019-07-22
Fecha Fin: 2022-08-31

Líder del proyecto

TECHNISCHE UNIVERSITEIT EINDHOVEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 170K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Our limited understanding of angiogenesis, the process leading to the formation of new blood vessels from pre-existing ones, hinders the design of new treatments for associated diseases such as cancer, ischemia, and diabetic retinopathy. It is well established that sprouting angiogenesis involves a process of endothelial cell phenotype selection mediated by the interaction between vascular endothelial growth factor (VEGF) and Notch signalling. Recently, it has been demonstrated that the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ), the main mediators of the Hippo signalling pathway, interact with VEGF and influence Notch signalling. However, it is still unclear how the effects of YAP/TAZ on Notch signalling contribute in regulating angiogenesis. In this project, I will adopt an approach combining experimental and computational techniques. First, I will culture endothelial cell monolayers on differently stiff substrates and I will perturb Notch via ligand-coated beads and YAP/TAZ activity via pharmacological inhibition. With the information deriving from these experiments, I will develop a unique agent-based computational model for angiogenesis, accounting for the interplay between Notch and YAP/TAZ. I will use this model to predict the effects of the Notch-YAP/TAZ crosstalk on angiogenesis. Finally, I will adapt previously established in vitro experimental systems recapitulating angiogenesis in three-dimensional environments. In these systems, I will vary the matrix stiffness, inhibit YAP/TAZ activation, perturb Notch signalling with ligand-coated beads, and measure the changes to parameters such as sprout and branch density and the dynamics of individual cell behaviour. This interplay between experimental and computational techniques will enhance our understanding of the crosstalk between Notch and Hippo-YAP/TAZ in regulating angiogenesis, with the potential to inspire new medical treatments.

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