Intracellular Controlled Radical Polymerizations

Lead Research Organisation: University of Strathclyde
Department Name: Pure and Applied Chemistry

Abstract

The interface of synthetic biology and (bio)materials is a highly promising, yet underexplored field of research. It can play a key role in addressing one of the biggest questions to mankind, which is how life started and how non-living materials became living. If synthetic polymers are successfully integrated into living cells, it will become feasible to induce effects within cells by bio-orthogonal triggers, thereby, opening up new avenues to gain control over cells, i.e. over their development and behavior.
The overarching goal of this project is to integrate biocatalytic controlled radical polymerizations (bioCRP) into living cells as a fundamentally new approach to interface biological systems with synthetic polymers and polymeric nanostructures. This project aims to achieve a fundamental understanding of what happens when amphiphilic block copolymers are synthesized and self-assembled directly within cells, and how this process can be steered to form nanostructures or semi-synthetic cell membranes. To this end, methods for intracellular bioCRP and polymerization-induced self-assembly will be developed and the intracellular self-assembly of block copolymers and their integration into the cell membrane will be studied.

Publications

10 25 50
 
Description The award was continued as award EP/V047035/2, which is still running until May 2023. Therefore, key findings and results will be reported under grant EP/V047035/2 once that grant has come to an end.
Exploitation Route The award was continued as award EP/V047035/2, which is still running until May 2023. Therefore, outcomes to be used by others will be reported under grant EP/V047035/2 once that grant has come to an end.
Sectors Chemicals,Manufacturing, including Industrial Biotechology

 
Description The award was continued as award EP/V047035/2, which is still running until May 2023. Therefore, outcomes that contribute to non-academic impacts will be reported under grant EP/V047035/2 once that grant has come to an end.
Impact Types Policy & public services

 
Description Intracellular Controlled Radical Polymerizations
Amount £74,652 (GBP)
Funding ID EP/V047035/2 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 02/2022 
End 05/2023
 
Description PhD Studentship to Eleonora Ornati
Amount € 140,198 (EUR)
Organisation Technical University of Darmstadt 
Sector Academic/University
Country Germany
Start 01/2022 
End 12/2024
 
Description Strathclyde Research Studentship Scheme - Student Excellence Award to Eleonora Ornati: "Enzymatic Synthesis and Self-Assembly of Block Copolymers within Living Cells"
Amount £30,000 (GBP)
Organisation University of Strathclyde 
Sector Academic/University
Country United Kingdom
Start 06/2021 
End 12/2021
 
Title Data for: "Peroxidase Activity of Myoglobin Variants Reconstituted with Artificial Cofactors" 
Description The data set contains CD spectra, ICP-MS data, native MS data, redox potential measurements, data of enzyme kinetic assays, and UV-vis spectra of the experiments presented and discussed in the Research Article: Guo, C.; Chadwick, R. J.; Foulis, A.; Bedendi, G.; Lubskyy, A.; Rodriguez, K. J.; Pellizzoni, M. M.; Milton, R. D.; Beveridge, R.; Bruns, N.. Peroxidase Activity of Myoglobin Variants Reconstituted with Artificial Cofactors. ChemBioChem 2022, 23, e2022001. https://doi.org/10.1002/cbic.202200197. The data has been deposited as text files or CSV files of the raw data wherever possible. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact Scientific paper ChemBioChem 2022, 23, e2022001. https://doi.org/10.1002/cbic.202200197. 
URL https://pureportal.strath.ac.uk/en/datasets/data-for-peroxidase-activity-of-myoglobin-variants-recon...
 
Description Enzymatic Polymerization in Aqueous Multi-Phase Systems 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution In the collaboration, we study the polymerization activity of enzymes in aqueous multi-phase systems. This will open up new opportunities in the realm of artificial cells and biotechnology. Both collaborators have the expertise of the individual parts of the project, i.e. aqueous multi-phase systems and enzyme partitioning (Schmidt) and enzymatically catalyzed polymerizations (Bruns).
Collaborator Contribution In the collaboration, we study the polymerization activity of enzymes in aqueous multi-phase systems. This will open up new opportunities in the realm of artificial cells and biotechnology. Both collaborators have the expertise of the individual parts of the project, i.e. aqueous multi-phase systems and enzyme partitioning (Schmidt) and enzymatically catalyzed polymerizations (Bruns).
Impact No output yet.
Start Year 2022
 
Description TU Darmstadt Centre for Synthetic Biology 
Organisation Technical University of Darmstadt
Department Department of Biology
Country Germany 
Sector Academic/University 
PI Contribution I have become a member (PI) of the Centre for Synthetic Biology at the Technical University opf Darmstadt (https://www.tu-darmstadt.de/synbio/synbio/mitglieder_1/index.en.jsp), and thus my research activities in the field of polymer-cell hybrid systems, as funded through this EPSRC grant, contribute to the research of the collaborative research centre.
Collaborator Contribution The interdisciplinary centre integrates expertise from the faculties of biology, chemistry and electrical engineering and information technology, material sciences and physics, mechanical engineering and social sciences. Synthetic biology is an engineering approach to equip biological cells with new molecular properties and features. In contrast to conventional biotechnology, this functionality is achieved by combining well-characterised and standardised components at the molecular level. New molecular biology methods, such as versions of the CRISPR gene scissors, are used in the process. Simultaneously, our ability to design RNA molecules and proteins for specific targets is rapidly evolving. In an abstract sense, synthetic biology thus combines defined elements to create a novel technological substrate that allows functional realisation for highly diverse purposes. The possible applications cover a very wide range: intelligent biosensors for in vitro or point-of-care diagnostics, the production of complex chemical compounds, the production of optimised proteins, e.g. enzymes, new (biocompatible) materials, new regulatory mechanisms for more robust plants and microorganisms and the generation of electrical energy. Within the Centre research is distributed over 3 levels: 1. molecular level (DNA, RNA, protein, nanopores) 2. cellular level (gene regulatory circuits, sensing, metabolic engineering) 3. multicellular level (synthetic organs, 3D-bioprinting)
Impact First reserach collaboration with other members of the Centre for Synthetic Biology have started, and have also lead to secure first internal funding (See Funding Research Field Matter and Materials: "Packaging bioactive molecules in artificial particles for controlled cellular effects"; PI: Prof. Ulrike Nuber, Co-PIs: Prof. Nico Bruns, Prof. Annette Andrieu-Brunsen)
Start Year 2022