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Description
Many cancer cell lines have been found to exhibit multiple structural and numerical aberrations of chromosomes – a condition known as ‘aneuploidy’ and most tumor types are predicted to be the same. It is not yet exactly understood why aneuploidy occurs but increasing evidence suggests that cells which abnormally develop more than two complete sets of chromosomes are likely to finally become aneuploid cells. These mechanisms are intimately intertwined with various cellular processes involved in the regulation of the cell cycle, such as the physical separation of the two daughter cells in the final step of the cell division, the self-killing of cells that malfunction, the internalization of external objects, such as synthetic nanoparticles, and others. Many aspects of these mechanisms and cellular processes are however still poorly defined because an important number of their defining components and properties are not accessible to standard imaging techniques and approaches. This project aims to combine complex optical and photonic approaches with sophisticated machine learning methods to achieve an innovative multimodal prototype nanoscope. This will offer easy operation and flexibility for imaging the structure and chemistry of cells in 2D & 3D based on complementary state-of-the-art and novel imaging techniques, providing unprecedented possibilities for cell imaging. The two partners will involve this prototype system, together with other already existing systems for nanoscale imaging, to implement a series of experiments focusing on questions still pending to be answered concerning the cell life and fate, with emphasis on aneuploidy. The novel research perspectives to be enabled by this project will be important for developing novel cancer diagnostic, prevention and therapeutic solutions that exceed current ones in terms of efficiency and ease of implementation. Other high-impact applications of this systems in life and materials sciences will be as well explored.
Summary of project results
Many tumor cell lines have been found to have an abnormal karyotype with multiple structural and numerical aberrations of chromosomes – a condition known as ‘aneuploidy’ and most tumor types are predicted to be the same. It is not yet exactly understood why aneuploidy occurs but increasing evidence suggests that unscheduled polyploid cells (cells having more than one pair of homologous chromosomes) can act as intermediates on the road to aneuploidy. Unscheduled polyploid cells can arise by several mechanisms such as cell fusion, mitotic slippage, failure to undergo cytokinesis or the generation of micronuclei due to improper nuclear envelope assembly. These mechanisms are intimately intertwined with other cellular processes involved in the regulation of the cell cycle, such as endocytosis or autophagy. Many aspects of these mechanisms and cellular processes remain however poorly defined to date because an important number of their defining components and properties are not accessible to standard imaging techniques and approaches. Furthermore, many open questions still exist on variousfundamental questions in cell biology due to the absence of appropriate optical characterization techniques or of efficient strategies for combining current techniques. Resolving these important questions requires novel imaging and data processing approaches.
To address pending challengesin cell biology the MEDYCONAI project combined complex optical, photonic and mechatronics approaches with sophisticated machine learning methods to develop an innovative system for multimodal imaging system, INTELINANO, taking the form of a tabletop, multimodal prototype nanoscope that offers easy operation and flexibility for imaging of the structure and chemistry in both 2D and 3D. It incorporates a variety of complementary imaging techniques, operating in the farfield and near-field regimes, providing unprecedented possibilities for the label-based and label-free characterization of cells at micro- & nanoscale resolutions. This combination of technologies opens new avenues towards advancing the understanding on cells at nanoscopic scales. In parallel to the technical developments, the two partners implemented experiments tackling fundamental questions that revolve around cell life and fate and will continue these efforts by exploiting the vast potential of INTELINANO. Important focus has also been placed on investigating via complex imaging approaches, complementing diverse assays of distinct kind, important aspects involved in the action of theranostic nanomaterials targeting cancers. Alongside this main body of efforts, the advantages of micro and nanoscale imaging have been as well put to work to shed light on relevant interactions between therapeutic nanomaterials and prokaryotic cells.
The multimodal INTELINANO prototype nanoscope, offering complex advantages for imaging the structure and chemistry of biological samples and advanced materials, developed in the project, represents a valuable resource for both life and materials scientists. It allows cells biologists to probe important cell processes via diverse contrast mechanisms complementary to fluorescence, the main workhorse in cell biology, overcoming intrinsic limitations related to fluorescence labeling. It allows materials scientists to probe and resolve important nanomaterial-cell interactions, such as internalization routes, therapeutic mode of action, unwanted effects, etc. The open-architecture of the INTELINANO prototype is also a highly useful result for optical & photonic engineers, given that it allows easy scaling up with additional workmodes, relying on a highly flexible architecture, and being comprised of optical and opto-mechatronic components that can be easily repurposed, to test new ideas and implement potential novel workmodes. Furthermore, the project activities contributed to the development of novel (mainly cancer focused) theranostic nanomaterials, and to new body of knowledge related to nanomaterials – cells interactions. This will be of great benefit to stakeholders in nanomedicine, but also the the consortium partners, who will continue collaborative work on this topic, in partnership with teams at the forefront of nanobiomaterials.
Summary of bilateral results
The collaboration between the team of the Center for Microscopy – Microanalysis and Information Processing at Politehnica Bucharest in Romania, and the Department of Molecular Cell Biology at the Oslo University Hospital in Norway significantly trengthened bilateral cooperation by fostering interdisciplinary collaboration, enhancing research capabilities, strengthening institutional relationships, advancing shared goals, and building trust and long-term relationships. This partnership not onlyadvanced scientific knowledge but also laid a strong foundation for future collaborative endeavors. The Romanian team''s expertise in optical and photonics engineering combined with the Norwegian team''s cell biology knowledge created a powerful interdisciplinary synergy. This enabled the development of novel imaging methods and protocols that neither team could have achieved alone. By pooling resources and sharing advanced equipment, both teams enhanced their research capabilities. The correlative nanoscope developed through this collaboration provides both teams with a state-of-the-art tool that will be highly relevant to conduct high-impact joint research for long time ahead. Team members from bothcountries had the opportunity to learn new techniques and methodologies from each other, expanding their skill sets and knowledge bases. Publishing joint research papers showcased the successful collaboration and elevated the profiles of both teams in the global scientific community. Jointly applying for research grants demonstrated the strength of the partnership and, will hopefully, provide financial support for ongoing and future projects. The success of this initial collaboration likely paves the way forfuture joint projects