Periodic Reporting for period 1 - BIOMOLMACS (Molecular Machines Functioning in Cells) Reporting period: 2020-01-01 to 2021-12-31 Summary of the context and overall objectives of the project The project BIOMOLMACS aims to establish a multidisciplinary training network on the emerging topic of molecular machines. The incorporation of the molecular machines in devices with application has an important potential. For this purpose, the molecular machines are integrated in mesoscopic assemblies by employing well-defined polymeric components with structural and functional control in this project. In particular, sequence controlled polymers have greater possibilities in the precise formation of nanoparticles such as polymersomes, and even support the generation of artificial cells. Hence, the combined molecular toolbox of molecular machines and precisely designed synthetic macromolecules will support the design of devices with innovative nanomedical application potential. The main BIOMOLMACS training objective is the education of the next generation of bionanotechnology researchers, who can apply advanced synthetic and analytical tools for the design of targeted polymeric biomedically active compounds in their future positions. The BIOMOLMACS project has four important objectives; development of molecular machines, design of artificial cells, understanding biophysics, and drug/gene delivery to living cells, which will be addressed collectively by the entire network. This interdisciplinary network has a unique structure for the training of ESRs and they are provided a complementary training on several aspects of chemistry, biology, and materials science, e.g. organic, and supramolecular chemistry, polymer chemistry, cell biology and biomaterials. The BIOMOLMACS training activities and scientific publications related to these objectives add scientific value through molecular machines functioning in cells for further exploitation by the planetary community. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far In this period, first and second-generation molecular machines and motors have been designed successfully by ESR1, ESR2, and ESR3. The detailed analytical characterization of the obtained molecular machines and motors has been done by using different analytical techniques. The modification of these machines and motors with sequence-controlled block glycopolymers prepared by ESR4 and ESR5 is still carried out. Afterwards, this sugar modified molecular machines and motors will be tested for specific cell targeting. The enzyme catalase stomatocytes with directional and rotational control have been developed and analyzed by ESR6 and ESR7. The surface decorations of these polymersome and stomatocytes with molecular machines and glycopolymers are still in progress. ESR8 has been using a microfluidic system to prepare different functional artificial cells. ESR9 who is in close collaboration with ESR6 and ESR7 prepared different types of polymeric materials to create bowl-shaped polymersomes and stomatocytes. Amphiphilic polymers have been synthesized and converted to nanoparticles successfully by ESR10 for potential use in drug and gene delivery. Furthermore, the biophysical properties of lipid-based membranes have been analyzed using DNA origami technology by ESR11. The first results were published in an open access scientific journal. ESR12 has succeeded to encapsulate different artificial organelles in larger polymer compartments in order to investigate their activities in the cell environment. The manuscript is under preparation to publish in a scientific journal, too. Additionally, ESR13 succeeded in generating two mitochondrially-targeted polypeptide-based drug delivery platforms in this period. Concerning the compounds with a theoretical endocytic pathway, the preliminary results provide evidence for the mitochondrial colocalization of our trivalent compound and suggest that triphenyl phosphonium (TPP) provided better targeting of polyornithine (PLO) than SS31 peptide. A library of liposome formulations to optimize the stability, uptake, location and RNA transfection were designed by ESR14 and also glycopolymers were incorporated to these liposomes to increase their cell selectivity. ESR15 is carrying out an industrial-based PhD on the implementation of efficient controlled polypeptide-based carrier synthesis under validated technologies. The synthesis of hydroxyproline NCA was scaled up successfully by two-step reaction with diphosgene and cyclization. Regarding the dissemination and exploitation activities, the first dissemination and exploitation plan of the BIOMOLMACS project has been designed. The social media accounts such as, facebook, twitter, Instagram, etc. were opened and used actively. The training lectures were posted on these social media accounts to access everyone. The training courses were captured and uploaded on the project website. They are made openly available on the project website and YouTube channel dedicate to BIOMOLMACS project. The first scientific data was published as an open-access research article on The Journal of Physical Chemistry B. All ESRs prepared short videos to describe their projects, show their facilities and working environments. These videos were uploaded on the BIOMOLMACS website, Instagram and YouTube channel. 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) The BIOMOLMACS programme offers immediate benefits to both the individual researchers and the training partners involved. These include promising career prospects in a growing biopharma and biomaterials market for the ESRs in the short term and direct research results to be exploited by the academic and industrial partners. All ESRs are developing networks through local interactions with other researchers at the host and secondment institutions. The complementary activities of the BIOMOLMACS project ensures that the expected impact is met. However, as there were many restrictions in normal life due to the COVID-19 pandemic, the impact of the actions was achieved partially. Even though the significant progress has been done in work packages, the outcomes such as, publication, presentation, patent, etc. are showing up recently. The first article was published, and more articles are in preparation. These studies have been collected in the deliverables summarised in this document. All Academics and Companies in the Network The Network Details Research related work packages in the Network The research projects being worked by ESRs All ESRs working in the Network
