Biochemistry
Under the direction of Prof. Dr. Christian Ungermann, the Biochemistry division investigates cellular transport processes in the model organism Saccharomyces cerevisiae (baker’s and brewer’s yeast). The research focuses on the molecular mechanisms underlying the transport of proteins and organelles to the cell’s digestive compartment — the lysosome. The proteins involved in these processes are analyzed to elucidate their roles in cellular growth and metabolic adaptation
Why do our cells need lysosomes?
Yeast cells, like our own, are enclosed by a membrane — the plasma membrane — that separates the cell’s interior from its environment. Only substances for which a specific transport protein exists can cross this boundary. In addition, cells contain membrane-bound organelles where metabolic reactions occur. Among these organelles are lysosomes in human cells and their functional counterparts, the vacuoles, in yeast. These organelles are the central focus of research in the Ungermann lab.
Lysosomes maintain cellular health by degrading and recycling cellular materials. Their interior, the lumen, is acidic and contains enzymes that can break down macromolecules such as proteins into their basic building blocks. The amino acids generated from lysosomal protein degradation are reused in the cytosol for the synthesis of new proteins.
Lysosomes recycle cellular material and support growth
How and why do proteins and organelles get into the lysosomes? Depending on nutrient availability and metabolic needs, cells selectively package proteins and organelles into membrane-enclosed vesicles. These vesicles then fuse with lysosomes, where their contents are degraded as described above.
In the Ungermann lab, research focuses on the proteins that mediate vesicle transport and fusion with lysosomes. For example, cells adapt their plasma membrane composition in response to nutrient conditions. When amino acid levels are sufficient, the corresponding transporters are removed from the cell surface, packaged into vesicles, and delivered to the lysosome for degradation. Through such adaptive mechanisms, cells ensure optimal conditions for growth at all times.
Autophagosomes deliver defective proteins and organelles to lysosomes
When cells cannot take up sufficient nutrients and experience starvation, they adjust their metabolism to generate new amino acids. Autophagy plays a key role in this process. During autophagy, marked cellular components — such as organelles or protein aggregates — are enclosed by a membrane to form an autophagosome. The autophagosome then fuses with the lysosome, allowing the degradation of damaged proteins and organelles and the recycling of their components into amino acids.
In the Ungermann lab, we reconstitute the formation and fusion of autophagosomes in vitro using artificial vesicles, providing detailed biochemical insight into these processes.
Molecular insights into protein structures explain their function
How can the function of lysosomal proteins be elucidated? The Ungermann group combines cellular analyses with studies on purified proteins and vesicles, developing novel assay systems to investigate their activity and regulation.
Research focuses on several lysosomal proteins and protein complexes, including the regulatory GTPase Rab7, its activator Mon1–Ccz1, the Fab1 lipid kinase complex, and the Atg2–Atg18 complex, which transfers lipids to growing autophagosomes. A central lysosomal tethering machinery is the HOPS complex, which resides on lysosomal and vacuolar membranes and mediates fusion with vesicles and autophagosomes.
Structural studies using cryo-electron microscopy, together with biochemical characterization, have deepened our understanding of HOPS function and its counterpart CORVET (in collaboration with the Möller group in Osnabrück). Structural and functional analyses of such key protein complexes are essential for uncovering the molecular causes of lysosomal diseases.
Yeast as a model system
Yeast as unicellular eukaryotes are remarkably similar to human cells. Fundamental cellular processes such as secretion and autophagy were elucidated through genetic analyses in yeast — work that has been recognized with Nobel Prizes (e.g., 2013 – Randy Schekman for identifying SEC genes in secretion; 2016 – Yoshinori Ohsumi for discovering ATG genes in autophagy).
