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Engineering translation machinery to produce light-responsive protein-polymers

Objective

A general and versatile technology to engineer visible light-responsive biological agents will enable spatio-temporal manipulation and interrogation of proteins, pathways, and cells, and the design of “smart” biomaterials that can direct and respond to biological processes on-demand. Site specific incorporation of multiple visible-light-responsive chemical groups at the polypeptide level will constitute a universal methodology for precise production of light-responsive proteins and protein-based materials. However, inadequate engineering of the protein translation apparatus limits the number and complexity of chemical groups that can be incorporated into proteins as synthetic amino acids (sAAs). This limitation precludes the incorporation of recently discovered visible-light-responsive chemical groups, hinders protein engineering efforts, and excludes production of biomaterials in which multiple identical sAAs provide new physical or biophysical properties. We propose to overcome this challenge by generating a genomic-engineering based platform for co-evolution of multiple components of the translation machinery (the aminoacyl tRNA synthetase, tRNA, and elongation factor) to select for cellular machinery capable of multi-site incorporation of highly substituted azobenzenes with a range of biologically relevant photochemical properties. We will then utilize these translation systems to produce libraries of azobenzene-containing protein-based materials to elucidate the sequence-function requirements for directing light-responsive self-assembly of macromolecular structures, and to generate biomaterial formulations for control of various intra- and extra-cellular processes. By developing and marrying technologies in synthetic biology, chemistry, and biomaterials, this study will enable the synthesis of light-responsive proteins, deepen our understanding of natural and evolved translation systems, and create new classes of functional light-responsive biomaterials.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2017-STG

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Host institution

BEN-GURION UNIVERSITY OF THE NEGEV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 328 712,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 328 712,00

Beneficiaries (1)

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