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Cell-free synthesis and assembly of biomolecular condensates: Engineering properties, functions and regulation

Project description

Engineering biomolecular interactions for cell-free applications

Cells are crowded environments and to increase efficiency of biological processes, the required components are concentrated in confined compartments. Further compartmentalisation of biological processes is achieved by the intrinsic capacity of many biomolecules to cluster in dense assemblies known as biomolecular condensates. These condensates enhance molecular interactions, allowing for the formation of highly specific and efficient biochemical reactions. Funded by the European Research Council, the SYNSEMBL project aims to engineer new biomolecular condensates as synthetic compartments in cell-free reactions. Researchers will employ microfluidics and produce tailored condensates with specific properties and functions. Ultimately, these biomolecular condensates have potential applications in material science and synthetic biology.

Objective

Compartmentalization is a defining characteristic of life and has the potential to enable and improve engineered manufacturing routes in biotechnology. Many biomolecules like proteins and RNA have the ability to spontaneously cluster in molecularly dense, phase-separated liquid-like assemblies, termed biomolecular condensates. Biomolecular condensates are promising as synthetic compartments in cell-free reactions and living cells because they could provide programmable, self-assembled spatial organization and rapidly appear or dissolve on demand. However, we are still lacking key engineering and characterization tools, a fundamental understanding of how the unique material properties influence internal biochemistry, and strategies to regulate these dynamic molecular assemblies. I have recently discovered that different condensate-forming proteins can be synthesized and assemble into liquid-like droplets in cell-free transcription and translation reactions run in a custom-designed microfluidic device. This project will pioneer cell-free synthesis for the engineering and characterization of biomolecular condensates, and engineer new synthetic compartmentalization strategies for cell-free systems and living cells. First, developing and taking advantage of a highly controlled microfluidic cell-free environment we will generate and characterize new synthetic compartments with tailored properties. Secondly, we will specifically target molecules and reactions into the condensate phase and systematically study how condensate properties influence biological functions. Finally, we will implement dynamic feedback control mechanisms that can autonomously adjust presence and functions of synthetic compartments in cell-free systems and in cells. SYNSEMBL will break new grounds for applications of biomolecular condensates in material science and synthetic biology.

Host institution

TECHNISCHE UNIVERSITAET MUENCHEN
Net EU contribution
€ 1 500 000,00
Address
Arcisstrasse 21
80333 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 500 000,00

Beneficiaries (1)