Control of epigenetic states through light-triggered protein-protein interaction mediators

• Applicant: Professorin Dr. Olalla Vazquez
• Subject Area: Biological and Biomimetic Chemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 439670201

Epigenetics is used to describe chromatin-based processes that dynamically regulate gene expression without altering the DNA sequence. In the last decade, there have been important breakthroughs in the understanding of some of the mechanisms underlying the epigenetic phenomena at the molecular level. Furthermore, the more we learn about epigenetics and its key role of in a plethora of human diseases, the more we realize of its potential for clinical medicine. However, targeting the epigenome meets challenges due to the difficulties in achieving both high selectivity and avoiding off-target effects. Thus, a particular protein may exert its function in a specific tissue or even at a precise growth stage of the cell, where it participates in an array of interactions, but the same protein may then be involved in different recognition process at some other time and place or even may not be functional at all. Light-responsive biologically active compounds provide the possibility to exert spatiotemporal resolution and in turn, to decipher cellular functions. Epigenetics photoswitches will offer new possibilities, extending the properties of chemical compounds and reversibly controlling molecular functionality bypassing the delivery of genes into the target cells. Therefore, our aim in this proposal is the development of conceptually innovative chemical approaches to achieve conditional and selective epigenome modulation by using nothing but small molecules and visible light. In particular, and taking into account the importance of protein-protein interactions in epigenome regulation, we devise the use of photo-responsive peptidomimetics as non-invasive tools to perturb these networks and modulate the epigenome. Such chemical approaches will provide complementary strategies to the biological ones, and lead to a better understanding of molecular details of epigenetic processes, as well as provide the basis for the discovery of novel therapies. In fact, our long-term goal is to translate our probes into therapeutically-relevant modulators of epigenetic processes.

• DFG Programme: Research Grants
• International Connection: Serbia, USA
• Cooperation Partners: Professorin Yali Dou, Ph.D.; Professorin Dr. Katarina Nikolic