Protein biosynthesis

Ribosomes are small nanomachines that carry out the translation of mRNAs into the amino acid sequence of proteins. The production of these machines is the most energy-intensive process in the cell and is therefore closely coordinated with cell growth and cell division. We want to understand in detail how cells can assemble new ribosomes from ribosomal RNAs and ribosomal proteins. In particular, we want to elucidate the role of AAA-ATPases and RNA helicases in this process. To this end, we use a broad spectrum of biochemical and biophysical methods including cryo-EM. Since the assembly of ribosomes is also a promising target for anti-tumor chemotherapy, we are also working on the development of drugs that specifically inhibit this process.

In eukaryotic cells, ribosome synthesis is a highly complex process. It involves not only the later constituents of the ribosome, the ribosomal proteins and ribosomal RNA, but also numerous auxiliary proteins known as ribosome assembly factors. A critical step in this process is the safe and efficient transport of newly synthesized ribosomal proteins from the cytoplasm to the nucleus, where ribosome synthesis begins. Our research focuses on uncovering the mechanisms of ribosomal protein import into the nucleus and the protective role of chaperones during this transport. We're also dedicated to identifying previously unknown ribosome assembly factors and understanding their functions. Lastly, we investigate how post-translational modifications, such as phosphorylation and methylation, regulate the functions of ribosomal proteins and assembly factors.

We explore how RNA helicases drive eukaryotic ribosome assembly. These versatile enzymes facilitate remodeling and folding of particularly complex rRNA regions, and release protein assembly factors and snoRNAs from emerging pre-ribosomes. They work alongside specific cofactors that regulate helicase-activity and guide them to their substrates during the assembly process. We decipher the molecular functions of RNA helicases through a variety of protein- and RNA-biochemistry methods coupled with structural investigations by cryo-electron microscopy.