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Biologically Inspired Molecular Adhesives towards Multifunctional Biomaterials and Microreactors

Project description

Harnessing cell-like micro-reactors without walls

Compartmentalisation is a fundamental theme in biology and is typically achieved by membranes. Separating molecules via membrane-bound organelles serves a variety of important functions, among which is keeping structures that need to work together close for efficiency. However, increasing evidence suggests that membranes and physical barriers are not the only way this is done. Cells may form compartments via liquid-liquid phase separation of proteins and nucleic acids to coordinate critical functions. The EU-funded VELCROProtein project plans to mimic this process in the lab to enhance understanding and thus the ability to harness these open microreactors for applications in fields ranging from drug discovery to drug manufacturing.

Objective

Recombinant proteins, including enzymes and antibodies, have revolutionized many sectors of biochemistry and biotechnology. In this project I propose a groundbreaking technology to control the supramolecular assembly of proteins in space and time to better mimic cellular organization and create a next generation of protein “living” materials for biocatalysis and medicine.

The core idea is to mimic cellular multiprotein assemblies and microreactors on the bench, by compartmentalizing multiple proteins in space. Increasing evidence indicates that cells can coordinate crucial functions by forming membrane-less compartments via liquid-liquid phase separation of proteins and nucleic acids. Most of the proteins involved in this process consist of globular regions and disordered domains, which are enriched in specific aminoacids and pilot highly controlled self-assembly. In this project we will conjugate functional globular proteins with sequences that mimic the disordered biological domains and act as “molecular Velcros”, thereby coupling biochemical functions with phase separation in space and time. Using a combination of microfluidic technology and in silico analysis, we will develop sequences capable to control not only the dynamic process of phase separation but also the phenotype of the resulting compartments, including selective recruitment of molecules, physical properties and response to specific switches.

This project will deliver adaptive compartments with unprecedented control of composition, environment, biochemical function and stimulus-responsiveness, going towards the development of networks of open microreactors, superior enzymes for green chemistry as well as smart materials for drug delivery. Moreover, the results will generate new knowledge on natural supramolecular structures that are associated with both functional biology and aberrant aggregates involved in devastating disorders such as Alzheimer’s and Parkinson’s disease.

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

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-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2020-COG

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Host institution

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
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.

€ 1 998 496,00
Address
Raemistrasse 101
8092 Zuerich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 998 496,00

Beneficiaries (1)

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