Alterations in Spatial Chromatin Organisation in Cancer Cells by Protein Methyltransferase

Content of the project
Cancer represents a significant global health challenge, affecting millions of people around the world. Current cancer therapies often come with severe side effects and increase the risk of cardiovascular diseases. There is an urgent need for new knowledge and drugs to combat cancer effectively. Methylation, as an epigenetic regulatory system, presents a promising target for developing targeted cancer therapies. This project aims to explore the mechanisms by which the methyltransferase N6AMT1 influences various cellular functions, particularly in relation to cancer development. More specifically, we aim to investigate how N6AMT1 influences the spatial chromatin organization and thus the accessibility of the genome for functionally relevant molecules. Epigenetic regulation involves alterations in chromatin organization — specifically heterochromatin and euchromatin — through processes such as DNA methylation and histone modifications, including acetylation and methylation. To investigate this in more detail, we will employ single-molecule localization microscopy (SMLM) in conjunction with mathematical evaluation methods, including Ripley point distance statistics, Persistent Homology, Persistent Imaging, and Principal Component Analysis, along with established heterochromatic and euchromatic markers. SMLM will enable us to analyze differences in the patterns of specific fluorescence-labeled heterochromatin and euchromatin markers in the presence and absence of the N6AMT1 protein. This approach can reveal characteristic network-like changes in the overall chromatin organization within cell nuclei, allowing to define cellular states and correlate these states with chromatin organization parameters. Image analysis of phase separation using confocal microscopy and topological data calculations following SMLM data acquisition will further enhance our understanding. The specific aim of this project is to develop the collaboration with Prof. Dr. Michael Hausmann's research group at Heidelberg University, who has expertise in SMLM alongside mathematical evaluation methods. This project will strengthen the exchange of higher education cooperation between Germany and Estonia, resulting in long-term collaboration and high-quality research with prospective application of future projects.

This project of the Baltic-German University Liaison Office is supported by the German Academic Exchange Service (DAAD) with funds from the Foreign Office of the Federal Republic Germany.