ForceDelivery
Financiado
Mechanosensitive proteins as a pathway to mechano-targeted drug delivery
Biophysical research over the last two decades has revealed that an impressive number of mechanical signals are key regulators of cell behavior. So far, the focus has been on understanding fundamental mechanosensing and transducti...
Biophysical research over the last two decades has revealed that an impressive number of mechanical signals are key regulators of cell behavior. So far, the focus has been on understanding fundamental mechanosensing and transduction mechanisms in health and disease. As increasing numbers of molecular players and signalling pathways are identified, the time has come to utilize this knowledge for diagnosing and treating diseases where mechanical processes play a role. In this proposal, I aim to target integrins to deliver reporter molecules and drugs to cells with a distinct mechanical phenotype. Integrins are transmembrane receptors through which cells can sense, transmit and discriminate biomechanical forces. During cell adhesion and migration, integrins engage with specific ligands in the extracellular matrix and undergo integrin recycling through continuous endo- and exocytosis. This known endocytic pathway, integrin clustering during adhesion and overexpression in disease states has made integrins a prime target for drug delivery. However, the chemical and physical factors governing integrin-mediated uptake of drugs and their intracellular fate are unknown. I propose to utilize molecular force sensor (MFS) technology to deconvolute the key factors in integrin-mediated drug delivery. Using rational protein design, a series of coiled coil MFSs with distinct chemical (charge and hydrophobicity) and physical (mechanical and thermal stability) properties will be produced. The molecular constructs will be appended with the integrin-targeting RGD motif, a fluorescent protein to investigate the intracellular fate and an actin-binding protein as a model drug that may potentially interfere with the cytoskeleton architecture. This MFS-based drug delivery system will enlighten the pivotal factors of integrin-mediated delivery, provide a diagnostic assay for discriminating cells based on their mechanical phenotype and open up the road towards mechano-targeted drug delivery.
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Duración del proyecto: 40 meses
Fecha Inicio: 2023-04-24
Fecha Fin: 2026-08-31
Fecha Fin: 2026-08-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-24
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2022-PF-01-01:
MSCA Postdoctoral Fellowships 2022
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
184K€
Líder del proyecto
UNIVERSITAT LINZ
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5