Biological pathways represent complex regulatory circuits within cells that are required to maintain a healthy cellular physiology. Aberrant regulation of these pathways leads to cellular dysfunction and the onset of diseases. Knowledge about the biomolecular drivers responsible for pathology is a major prerequisite to design strategies for a tailored treatment.
The field of chemical biology within our department combines multiple experimental approaches to decipher disease mechanisms and to manipulate them. Chemical probes are designed to identify disease-associated targets in whole cells and state of the art mass spectrometry-based technologies are used to mine the cellular proteome and metabolome. Proteins with crucial function in health and disease are subject to high-resolution analysis of their structure and dynamics using structural biology. Enzymes represent an important subclass of such proteins, as they are essential for catalytic transformations inside the cell. They can also be engineered for biocatalytic applications, which represent an attractive alternative to classical organic synthesis. Nucleic acids (RNA, DNA) are major players in gene regulation and cellular physiology and their dynamic interactions with proteins are studied by structural biology and biophysical methods. The mechanistic insights obtained on these biological macromolecules lay the foundation for the rational design of small molecules to manipulate biomolecular function in human diseases pathogenic bacteria or parasites.