Periodic Reporting for period 1 - PROGRAMED PROTOCELLS (Design and construction of programmed protocells for intercellular networks and biomimetic communications)
Reporting period: 2021-08-01 to 2023-07-31
The project “Programmable protocells for selective intercellular interactions and biomimetic communications” studies how synthetic cells or protocells can be constructed with an aim to produce specific functions or outputs. The current simplistic designs to build artificial cells limits their structural and organizational complexity and in turn their potential in applications. Employing concepts of bottom-up technology for the defined design and construction of complex synthetic constructs to generate programmable communities of protocells with the ability to sense, categorize, and process chemical signals collectively opens avenues to building life-like materials.
The intention behind the construction of these cell-like mimics is to understand the origin of life from non-living constituents and bridge the gap between chemistry and biology. The motivation for this project comes from understanding Nature. This field is of utmost importance for understanding the process behind evolution and the role chemistry plays in it.
Objectives of this Marie Skłodowska Curie Action (MSCA) is are) to design, develop, and construct self-organized protocellular communities that encapsulate intricate enzymatic reaction networks and capable of spontaneous and cooperative operation, akin to living cells behaviour, (ii) incorporating several essential functions within these protocellular communities such as the selective formation of protocellular consortia and mimicking critical biological functions, thereby enhancing the complexity of the protocellular constructs achieving proto-colonies, (iii) applying the principles of organic synthesis, supramolecular chemistry and out-of-equilibrium self-assembly to the interdisciplinary and evolving field of protocells. Ultimately, these research efforts intend to realize programmable protocells capable of active self-assembly, spatiotemporal self-sorting, self-regulation and higher-order organization and function. Overall, the aim is to push the boundaries of chemistry to understand and mimic biology. In parallel, the goal of the MSCA Individual Fellowship is to foster the personal growth and scientific independence of the Fellow (me).
The intention behind the construction of these cell-like mimics is to understand the origin of life from non-living constituents and bridge the gap between chemistry and biology. The motivation for this project comes from understanding Nature. This field is of utmost importance for understanding the process behind evolution and the role chemistry plays in it.
Objectives of this Marie Skłodowska Curie Action (MSCA) is are) to design, develop, and construct self-organized protocellular communities that encapsulate intricate enzymatic reaction networks and capable of spontaneous and cooperative operation, akin to living cells behaviour, (ii) incorporating several essential functions within these protocellular communities such as the selective formation of protocellular consortia and mimicking critical biological functions, thereby enhancing the complexity of the protocellular constructs achieving proto-colonies, (iii) applying the principles of organic synthesis, supramolecular chemistry and out-of-equilibrium self-assembly to the interdisciplinary and evolving field of protocells. Ultimately, these research efforts intend to realize programmable protocells capable of active self-assembly, spatiotemporal self-sorting, self-regulation and higher-order organization and function. Overall, the aim is to push the boundaries of chemistry to understand and mimic biology. In parallel, the goal of the MSCA Individual Fellowship is to foster the personal growth and scientific independence of the Fellow (me).
The research work corresponding to this project was achieved via 7 work packages (WP0-WP6). WP0 included the meetings to discuss the progress of the project, data management procedures etc. The bulk of this work package was completed in the initial days of the project. WP1 was involved with the design and synthesis of programmable artificial cells. Colloidal protocells and vesicular compartments were synthesized with semipermeable membranes. The walls of these compartments were modified by covalently attaching polymers on the surface. The pore sizes, scalability and wall type were deciding factors for design of these compartments. These protocells could potentially aggregate to form proto-colonies induced by environmental triggers. WP2 dealt with the interprotocellular communications between the binary populations of protocells which interact with each other. The leaky nature of these compartments was exploited to exhibit well-known enzyme cascade reactions between the interacting protocells via loading biologically essential proteins and enzymes in these artificial cells. Moreover, the compartments could be shown to interact and assemble following electrostatic, host/guest, protein/protein interactions to undergo programmable cell-cell signalling. WP3 is involved in the formation of switchable assembly states of the compartments. Enzymatically controlled trigger in the environmental pH conditions were shown to switch the interactions between protocells from docking to undocking states. This in turn affects the intercellular communications and as a result signalling. WP4 was involved in the development of redox homeostasis in artificial cells which was achieved through opposing enzymatic systems in interacting protocellular models. WP5 and WP6 focussed on the researcher training, transfer of knowledge and communication and dissemination of results.
During the work on research projects, the fellow has trained several masters (thesis defended in summer 2022) and bachelor (project report submitted in 2022 and 2023) students which has led to successful projects. She has also been involved in summer school and guidance of PhD students. The fellow has received training in the construction of various kinds of artificial cells and compartments like liquid-liquid phase separated coacervates, colloidosomes, capsules, giant unilamellar vesicles (at Prof. Stephen Mann’s Lab, School of Chemistry, University of Bristol), fluorescence and confocal fluorescence microscopy, also got training in handling living cells like yeast and bacteria. The project and results have led to many new fruitful collaborations which could lead to impactful research output in the near future.
Results of the fellow’s research will be reported in manuscripts (3 manuscripts in preparation, 2 projects which require some more supporting data), research seminars and conferences. This work has already been presented at two conferences (Syncell 2022 and Gordon Research Conference on Supramolecular Chemistry and Self-assembly 2023) via poster and invited oral presentations. Our research was also popularized by various research seminars where the outcomes were highly appreciated.
During the work on research projects, the fellow has trained several masters (thesis defended in summer 2022) and bachelor (project report submitted in 2022 and 2023) students which has led to successful projects. She has also been involved in summer school and guidance of PhD students. The fellow has received training in the construction of various kinds of artificial cells and compartments like liquid-liquid phase separated coacervates, colloidosomes, capsules, giant unilamellar vesicles (at Prof. Stephen Mann’s Lab, School of Chemistry, University of Bristol), fluorescence and confocal fluorescence microscopy, also got training in handling living cells like yeast and bacteria. The project and results have led to many new fruitful collaborations which could lead to impactful research output in the near future.
Results of the fellow’s research will be reported in manuscripts (3 manuscripts in preparation, 2 projects which require some more supporting data), research seminars and conferences. This work has already been presented at two conferences (Syncell 2022 and Gordon Research Conference on Supramolecular Chemistry and Self-assembly 2023) via poster and invited oral presentations. Our research was also popularized by various research seminars where the outcomes were highly appreciated.
This MSCA project aimed at the performance of interdisciplinary research towards understanding the intricacies behind the origin of life. The project has tried to push the boundaries of synthetic biology and synthesize artificial cellular constructs and assemble them to higher order aggregates and exhibit functional protocells which can exist synergistically. The innovative aspects covered in this project are using the concepts of chemistry and biology together to construct synthetic cells, implementation of various essential techniques like spectroscopic, microscopic etc. to gain better insights into the structure and functioning of the protocells and the collective operation of these compartments in their aggregate state. The results achieved in this project have gone above and beyond the proposed outcomes which could have important socio-economic impacts. The potential impacts expected from this project could have applications in basic research as well as applied research. The project aims towards the fields of medical science, environmental remedy, energy production which could potentially enrich the European technological developments. This fellowship outputs will add to the European competitiveness in synthetic biology as well. The Fellow’s research on programmable protocells and valuable novel understandings are emerging with respect to both design and development of new artificial constructs and knowledge generation.