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ProForce

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Mechano Regulation of Proteins at Low Forces Paving the Way for Therapeutic In...

Mechano Regulation of Proteins at Low Forces Paving the Way for Therapeutic Interventions Mechanical forces play critical roles in the regulation of biological functions, including development, motility, and haemostasis. Aberrant mechano-regulation is implicated in human pathologies, including cancer and infarction. Pr... ver más

28/02/2027

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

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

TRL 4-5

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-11-30

ERC-2020-COG: ERC CONSOLIDATOR GRANTS

I+D

Cerrada hace 4 años

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Información adicional privada

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

2 Participantes

1.99M€ | Lider

TEXNOVO, S.A.

999.53K€ | Participante

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Duración del proyecto: 62 meses Fecha Inicio: 2021-11-30
Fecha Fin: 2027-02-28

Líder del proyecto

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

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Mechanical forces play critical roles in the regulation of biological functions, including development, motility, and haemostasis. Aberrant mechano-regulation is implicated in human pathologies, including cancer and infarction. Proteins sense forces by undergoing conformational changes under external loads that trigger downstream signaling. Despite its importance, mechanical regulation at the single-protein level remains poorly understood, in part due to a lack of suitable techniques to probe the physiological highly relevant low force (~1 pN) range. ProForce aims to understand mechano-regulation at the single-molecule level in this previously inaccessible regime and to develop approaches to directly interfere with and correct aberrant force responses. We propose to advance massively-parallel magnetic tweezers as the ideal tool for single-protein force measurements, as they can resolve very small forces (<0.1 pN), perform stable and highly-multiplexed measurements over long times, and can readily be combined with fluorescence detection to provide an orthogonal read out. We aim to address three sets of biological systems that are regulated by low forces and are potential targets for drugs that alter their force response: 1) The blood protein von Willebrand factor (VWF) that is activated by shear flow and critically involved in haemostasis. Reduced VWF activity leads to bleeding disorders, while gain-of-function mutations increase the risk of myocardial infarction. 2) Focal adhesion kinase is a force-activated kinase involved in intracellular signal transduction pathways important in cell proliferation, migration, and metastasis. 3) Adhesion G-protein coupled receptors are a subset of the GPCR-family, activated by mechanical stimuli and involved in development, immunity, neuronal function, and tumorigenesis. The aim of ProForce is to understand mechano-regulation at the single-protein level and to establish force response as a potential drug target.

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