Description du projet
Nouvelle classe de cryoprotecteurs à base de protéines polymères
Des cryoprotecteurs efficaces et non toxiques sont essentiels pour le stockage à long terme de cellules et de tissus viables comme agents thérapeutiques en médecine régénérative. Les biopolymères, connus sous le nom de protéines qui se lient à la glace (IBP pour «ice‑binding proteins»), sont capables de prévenir les lésions dues à la congélation en empêchant la nucléation et la croissance des cristaux de glace. Le projet PROTECT, financé par l’UE, vise à développer des IBP modulaires afin de réaliser les expériences physico‑chimiques quantitatives nécessaires pour comprendre ce qui régit l’activité des IBP en tant qu’inhibiteurs des lésions dues à la congélation au niveau de la molécule unique, et pour optimiser la cryoconservation. L’objectif est de synthétiser une nouvelle classe de polymères d’IBP et, à l’aide de la microscopie à super‑résolution, d’évaluer leur impact sur la cryoconservation des cellules et des tissus cardiaques.
Objectif
Efficient, non-toxic cryoprotectants, that allow long-term storage of viable therapeutic cells and tissues, are the tool that regenerative medicine requires for its successful realization into a viable therapeutic option. A remarkable class of biopolymers known as ice-binding proteins (IBPs) alleviate the risk of freeze injury throughout the Kingdoms of Life by keeping the nucleation and growth of ice crystals in check. Yet, the application potential of IBP analogues (IBPAs) as cryoprotectants has remained underexploited. This is because we are yet to unravel and utilize the structure-function relations, which govern the activity of IBPAs as inhibitors of ice recrystallization and promoters of ice nucleation at the single-molecule level in vitro and within a complex biological environment.
I propose to develop uniquely modular IBPAs to perform the quantitative single-molecule and physico-chemical experiments essential to bridge this knowledge gap and to engineer ice-binders optimized for cryopreservation. Our first aim is the biosynthesis of a novel class of ice-binding protein-polymers (iPP) with systematic variations in composition and size. Ice nucleators with a broad range of sizes will be created from iPPs of variable chain length by dissolution, self-assembly and surface-tethering to nanoparticles of variable dimensions. Super-resolution microscopy experiments of iPP ice-binding will deliver high-resolution maps of spatiotemporal distribution and dynamics. These will be related to iPP structure, physico-chemical properties, ice recrystallization inhibition (IRI) and ice nucleation (IN) activity. These insights will translate into the next generation of bioactive iPPs tailored to maximize both IRI and IN. Their impact on heart cell and tissue cryopreservation will be examined to advance our fundamental understanding of freeze injury and dramatically improve post-thaw recovery as well as structural and functional integrity without adverse effects.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
5612 AE Eindhoven
Pays-Bas