Dr. Sidney Becker

Max-Planck-Forschungsgruppenleiter

Die Prinzipien der molekularen Evolution

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Research Statement

Life’s genetic blueprint is encoded in DNA, which is transcribed into RNA and then translated into proteins. Life, however, depends not only on this linear transfer of information but also on its precise regulation across space and time. A regulatory information layer is established through chemical alteration of the four genetic building blocks. To date, around 40 DNA modifications and more than 170 RNA modifications have been identified.

These modifications alter the physicochemical properties of nucleic acids, affecting their stability, folding, and interactions with other biomolecules. Consequently, they are believed to regulate gene expression by modulating transcription, RNA processing, and protein synthesis. Extensive crosstalk among these fundamental processes creates multiple layers of control, ensuring precise and coordinated gene expression along the central dogma. This is essential not only for establishing cell-type-specific expression patterns that define cellular identity and function, but also for enabling cells to adapt to environmental stress through dynamic adjustments in gene expression.

The precise mechanisms by which epigenetic and post-transcriptional modifications orchestrate gene expression within a complex regulatory network remains poorly understood. However, distinct differences in modification profiles between healthy tissues and disease states underscore the critical role of their spatiotemporal deposition in normal human development, with dysregulation linked to pathology. It is essential to determine whether altered modification profiles contribute to dysfunction and pathology or if they are the result of redirected metabolic pathways.

Currently, most genetic modifications cannot be reliably profiled, preventing further progress in understanding their exact biological function. Therefore, comprehensive profiling of epigenetic and post-transcriptional modifications is key for deciphering gene regulation networks to uncover disease mechanisms, identify innovative drug targets, and establish novel biomarkers.

Our work centers on developing robust detection methods to investigate the distribution, dynamics, and interdependencies of DNA and RNA modifications, with the goal of clarifying their roles in gene regulation. To achieve this, we employ chemical, biochemical and molecular biology techniques to create innovative profiling methods. Currently, our research is focused on three main areas:

1. Highly sensitive methods for detecting rare genetic modifications
2. Novel strategies for the parallel profiling of multiple genetic modifications
3. Innovative approaches for de novo enzymatic DNA synthesis