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PITT-Inflame

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Platelet-derived Integrin- and Tetraspanin-enriched Tethers as key effectors in...

Platelet-derived Integrin- and Tetraspanin-enriched Tethers as key effectors in thrombo-Inflammation Platelets are mediators of haemostasis and thrombosis, but also increasingly recognized as versatile effector cells of innate immunity. The concept of thrombo-inflammation recognizes that thrombotic and inflammatory pathomechanism... ver más

30/09/2029

KLINIKUM DER BAYER...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITAETSKLINIKUM WUERZBURG KLINIKUM DER... 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 HORIZON EUROPE notifico la concesión del proyecto el día 2024-10-01

ERC-2023-ADG: ERC ADVANCED GRANTS Scope:Objectives

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KLINIKUM DER BAYERISCHEN JUL...

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Duración del proyecto: 59 meses Fecha Inicio: 2024-10-01
Fecha Fin: 2029-09-30

Líder del proyecto

UNIVERSITAETSKLINIKUM WUERZBURG KLINIKUM DER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Platelets are mediators of haemostasis and thrombosis, but also increasingly recognized as versatile effector cells of innate immunity. The concept of thrombo-inflammation recognizes that thrombotic and inflammatory pathomechanisms are closely intertwined. Platelets thereby act as central orchestrators of immune cell trafficking, vascular barrier function and organ integrity and contribute to organ injury in severe disorders with limited treatment options (e.g. stroke, sepsis, ARDS). The underlying molecular mechanisms are not known.I recently discovered an unexpected novel effector mechanism in platelets with potentially huge impact for understanding these cells in health and disease: Resting platelets can rapidly reorganize the entire pool of their principal adhesion receptor, integrin αIIbβ3, along with its associated tetraspanins and signalling machinery into ´disintegration´ complexes (DISCs) in distinct membrane microdomains. These DISCS serve as building blocks for a novel organelle, the ´Platelet-derived Integrin and Tetraspanin-enriched Tether´ (PITT). PITTs are loaded with signalling molecules, ribosomes and RNA and can segregate from the platelet to promote thrombo-inflammation. Also β1-integrins as well as glycoprotein (GP)VI can be integrated into DISCs and deposited at discrete adhesion points.I therefore postulate that circulating platelets have the capacity to use their principal adhesion/signalling machineries in two fundamentally different ways and thereby switch between the haemostatic and a thrombo-inflammatory effector programme. If proven correct, this would implicate a radically new paradigm in platelet biology, and open new avenues for the treatment of a wide range of diseases with major societal impact.PITT-Inflame will (i) provide a detailed molecular composition and architecture of DISCs and PITTs; (ii) decipher underlying signalling networks; (iii) identify PITT-induced effects on target cells and (iv) deduce therapeutic strategies.

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