Polymeric Membranes for Artificial Endosymbionts

Project Information

PolyMAE

Grant agreement ID: 101032493

DOI

10.3030/101032493

Project closed

EC signature date 16 March 2021

Start date 4 May 2021

End date 3 May 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 179 313,34

EU contribution

€ 179 313,34

Coordinated by

TECHNISCHE UNIVERSITAT DARMSTADT
Germany

Periodic Reporting for period 1 - PolyMAE (Polymeric Membranes for Artificial Endosymbionts)

Reporting period: 2021-05-04 to 2023-05-03

Summary of the context and overall objectives of the project

The MSCA “Polymeric Membranes for Artificial Endosymbionts (PolyMAE)” investigates a cutting-edge technique for encapsulating prokaryotes in biocompatible shells, aimed at the production of bio-orthogonal artificial endosymbionts. Endosymbionts are organisms that thrive within a host organism, usually in a symbiotic relationship. Notably, mitochondria and plastids such as chloroplasts in eukaryotic cells are considered to be endosymbionts of bacterial origin. Through mimicking nature's wisdom, synthetic biology is at the forefront in modifying the molecular biology of the host to incorporate other organisms, with the ultimate goal of developing entire genetic circuits and metabolic pathways.

Central to the PolyMAE project is the concept of artificial endosymbiosis. Encasing the 'guest' organisms in biocompatible polymers bolsters the prospects of achieving artificial endosymbiosis. The use of polymeric membranes ensures that the encapsulated organisms are protected and can effectively integrate with the host's biology.
Such advancements have far-reaching implications, particularly in the fields of medicine and biotechnology. For instance, the ability to produce artificial endosymbionts can revolutionize drug delivery systems, wherein encapsulated microorganisms can be engineered to deliver therapeutic agents directly to targeted cells.
Furthermore, in agriculture and environmental sciences, these artificial endosymbionts could be used to promote plant growth or mitigate environmental pollutants, through the establishment of beneficial relationships between the artificial endosymbionts and plant cells.
This research also fosters an interdisciplinary approach. It contributes to a broader understanding of the delicate interactions between different biological entities and how they can be harnessed for societal good. In summary, the PolyMAE project, funded by the Marie Skłodowska-Curie Actions programme, marks a substantial stride in the realm of synthetic biology. By exploring novel techniques for encapsulating prokaryotes within biocompatible polymeric membranes, it opens avenues for the production of artificial endosymbionts with potential applications in medicine, biotechnology, agriculture, and environmental sciences. This project is not just about scientific innovation but also represents an epitome of how principles of design and creative thinking can result in solutions that address global challenges and contribute positively to society.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the fellowship period, I embarked on a multi-faceted research project at the University of Strathclyde and Technische Universität Darmstadt under Professor Nico Bruns' supervision.

At first (WP1), I focused on the development of a method for encapsulating bacteria in polymeric membranes to create single bacteria-polymer constructs. This encapsulation was achieved by forming micrometer-sized polymer vesicles that would surround the bacteria. I achieved the initial goals by contributing to one publication (under peer review) and presenting findings at two conferences. This work has implications for biotechnology, medicine, and synthetic biology, particularly in the development of artificial endosymbionts.

The second research direction (WP2) aimed to encapsulate bacteria via enzymatic polymerization-induced self-assembly (bioPISA). Although the focus shifted from the initial objective, I developed enzyme-synthesized artificial cells in the form of polymeric vesicles. These vesicles could encapsulate biomolecules such as DNA and cell lysate and transform into active artificial cells capable of expressing proteins. The results are documented in an article under peer review, and I presented these findings at four conferences. In addition, I made progress in enzymatic polymerization from surface-expressed enzymes on yeast cells, functionalizing them with grafted polymers. This ongoing work has far-reaching applications in synthetic biology and presents innovative approaches for creating artificial cells and modifying yeast.

The results will soon be published in peer-reviewed jorunals, and have already been disseminated in 7 conferences.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Significant progress has been made in WP1 for developing a method for the encapsulation of bacteria into polymeric membranes. This achievement allows for the creation of single bacteria-polymer constructs that facilitate feeding to the encapsulated bacteria. The encapsulation method developed not only validates the process but also enables the decoration of the cell surface without genetic engineering. The findings have been published in a preprint article and highlight the increased toughness of E. coli cells through encapsulation in commercial block copolymers. This breakthrough lays the foundation for further research in developing single bacteria-polymer constructs with potential applications in biotechnology and medicine.

Although deviating from the original objectives, the research in WP2 has shown promising results in the field of enzymatic polymerization-induced self-assembly (bioPISA) for bacterial encapsulation. Collaborative efforts with other institutions have led to the development of enzyme-synthesized artificial cells (polymeric vesicles) capable of encapsulating biomolecules and transforming into active artificial cells that express proteins. These findings have been submitted for peer review and have been presented at several conferences, demonstrating their significance in the scientific community. Furthermore, preliminary results on bacterial surface grafting of polymers have led to the exploration of yeast as a viable alternative. Functionalization of S. cerevisiae cells through enzymatic polymerization shows potential for introducing phenotypical modifications. The ongoing research in enzymatic polymerization-driven vesicles and the decoration of yeast cells with polymers hold promise for the creation of artificial cells with groundbreaking applications in synthetic biology. Additionally, the ability to introduce new surface functionalities through yeast decoration has implications for sustainable and repeatable modifications across generations.

The progress made in these work packages expands the boundaries of current knowledge and opens up new avenues for research in synthetic biology, biotechnology, and medicine. The development of single bacteria-polymer constructs and enzymatic polymerization-driven vesicles has the potential to revolutionize various fields, offering innovative approaches and practical solutions. These advancements may have significant socio-economic impacts, contributing to the development of novel technologies, potential commercial applications, and advancements in healthcare. The wider societal implications include the potential for improved treatments, sustainable biotechnological processes, and the advancement of knowledge in the field of synthetic biology, ultimately benefitting society as a whole.

The principle for the production of polymeric artificial cells via enzymatic polymerization