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SynProAtCell

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Delivery and On Demand Activation of Chemically Synthesized and Uniquely Modifie...

Delivery and On Demand Activation of Chemically Synthesized and Uniquely Modified Proteins in Living Cells While advanced molecular biology approaches provide insight on the role of proteins in cellular processes, their ability to freely modify proteins and control their functions when desired is limited, hindering the achievement of a... ver más

30/09/2025

TECHNION ISRAEL I...

3M€

Presupuesto del proyecto: 3M€

Líder del proyecto

TECHNION ISRAEL INSTITUTE OF TECHNOLOGY No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2019-05-03

ERC-2018-ADG: ERC Advanced Grant

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.

2 Participantes

TECHNION ISRAEL INSTITUTE O...

2.50M€ | Lider

ULMA FORJA

1.63M€ | Participante

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Duración del proyecto: 76 meses Fecha Inicio: 2019-05-03
Fecha Fin: 2025-09-30

Líder del proyecto

TECHNION ISRAEL INSTITUTE OF TECHNOLOGY No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 3M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto While advanced molecular biology approaches provide insight on the role of proteins in cellular processes, their ability to freely modify proteins and control their functions when desired is limited, hindering the achievement of a detailed understanding of the cellular functions of numerous proteins. At the same time, chemical synthesis of proteins allows for unlimited protein design, enabling the preparation of unique protein analogues that are otherwise difficult or impossible to obtain. However, effective methods to introduce these designed proteins into cells are for the most part limited to simple systems. To monitor proteins cellular functions and fates in real time, and in order to answer currently unanswerable fundamental questions about the cellular roles of proteins, the fields of protein synthesis and cellular protein manipulation must be bridged by significant advances in methods for protein delivery and real-time activation. Here, we propose to develop a general approach for enabling considerably more detailed in-cell study of uniquely modified proteins by preparing proteins having the following features: 1) traceless cell delivery unit(s), 2) an activation unit for on-demand activation of protein function in the cell, and 3) a fluorescence probe for monitoring the state and the fate of the protein. We will adopt this approach to shed light on the processes of ubiquitination and deubiquitination, which are critical cellular signals for many biological processes. We will employ our approach to study 1) the effect of inhibition of deubiquitinases in cancer. 2) Examining effect of phosphorylation on proteasomal degradation and on ubiquitin chain elongation. 3) Examining effect of covalent attachment of a known ligase ligand to a target protein on its degradation Moreover, which could trigger the development of new methods to modify the desired protein in cell by selective chemistries and so rationally promote their degradation.

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