Project Code: RO-NO-2019-0601
Contract Number: 25/2021
Project Title: Understanding Membrane Dynamics and their Implications for Cancer with Correlative Optical Nanoscopy and Artificial Intelligence
Duration: 40 months (01/01/2021-30/04/2024)
Total project value: 1.647.385 EUR (Grant value: 1.177.935 EUR; Co-financing: 469.450 EUR)
Abstract:
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 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 micro-nuclei 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, two complex cellular programs through which cells regulate various aspects of their homeostasis. 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. Open questions are still on the table regarding many other fundamental questions of cell biology due to the absence of appropriate optical characterization techniques or of efficient strategies for combining current techniques. Resolving these important questions will require thus novel imaging and data processing approaches.
MEDYCONAI will address this situation by combining complex optical, photonic and mechatronics approaches with sophisticated machine learning methods to achieve an innovative system for multimodal imaging named INTELINANO, which will take 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. The developed prototype will incorporate complementary state-of-the-art and novel imaging techniques to provide unprecedented possibilities for the label-based and label-free characterization of cells at nanoscale resolutions. Furthermore, INTELINANO will exhibit intelligent capabilities for the automated analysis of combined complementary data sets, data forecast & data simulation based on novel Deep Learning approaches. This combination of technologies will advance the current level of understanding of optical data sets collected on cells at nanoscopic scales. The two partners will involve this prototype system to implement a series of experiments that will tackle fundamental questions that revolve around aneuploidy. Correlative imaging with label-based and label-free nanoscopy techniques of key membrane dynamics processes such as cytokinesis, nuclear envelope assembly, autophagy or endocytosis will lead to achieving a clearer picture of the reasons behind aneuploidy and will help decipher the interplay between different cellular processes and regulatory pathways related to this problem. This will be important for developing novel cancer diagnostic, prevention and therapeutic solutions that exceed current ones in terms of efficiency and ease of implementation. Last but not least, the knowledge and results generated in this project will play an important role in raising the awareness of stake-holders in imaging, biology and medicine over the huge potential held by correlative optical imaging with emerging techniques.
Objectives:
The objective of MEDYCONAI is to develop a multimodal prototype system, INTELINANO, that incorporates a variety of complementary techniques for super-resolved optical imaging, augmented by artificial intelligence, and to employ this powerful tool for expanding the current understanding of several key membrane dynamics processes of eukaryotic cells to resolve their role in the occurrence of aneuploidy. The project also has set as a main objective the development of novel methods and approaches based on emerging nanoscopy techniques, that will allow the better comprehending of biological species
Expected Results:
-novel techniques for super-resolved optical imaging
-integration of state-of-the art and novel super-resolved optical imaging techniques into a multimodal prototype system
-novel artificial intelligence methods for high-resolution 2D and 3D data analysis and augmentation
-development of novel approaches based on correlative nanoscopy for the in-depth understanding of biological species
-enhanced understanding of membrane dynamics and their role in cancer development
-novel research avenues based on correlative label-based and label-free imaging with the potential to resolve still pending questions concerning cell life
Funding Agency :
Executive Unit for Higher Education, Research, Development and Innovation Funding (UEFISCDI)