Although the vast majority of bacteria are innocuous, or even beneficial, to mammalian hosts, pathogenic bacteria are responsible for a number of important diseases. Bacteria manipulate several host cellular functions to ensure their survival and replication. Our research is focused on determining whether bacteria also interfere with the RNA metabolism of host cells, and to characterize how this may benefit or antagonize the bacterial life cycle. This knowledge will potentially lead to the development of novel therapeutic approaches against bacterial infection.

Production and secretion of the pro-inflammatory cytokine interleukin-1 (IL-1) is a highly regulated process. While the intracellular generation of IL-1 protein is well understood, we know little about how IL-1 is subsequently secreted. In contrast to most other secreted proteins, IL-1 is not automatically released after the protein is generated. Rather, it is retained in the cytoplasm until the cell receives a specific stimulus that activates intercellular complexes termed ‘inflammasomes’, which are required for IL-1 secretion. We study the mechanisms of inflammasome activation, and how inflammasomes orchestrate the subsequent secretion of IL-1.

Tobias Madl studies the molecular mechanisms by which intrinsically disordered proteins (IDPs) are acting as key regulators of cell and organismal fate, and how they contribute to diseases and ageing. To this end the group employs and develops a novel multidisciplinary approach in which Nuclear Magnetic Resonance spectroscopy, Small-angle X-ray/neutron scattering and modeling strategies are combined. This generates general knowledge on protein-protein interactions involving IDPs and provides insight into the intricate link between IDP function, regulation and human diseases.

The regulation of translation is critical for a large number of important cellular processes, however our understanding of the molecular mechanisms controlling translation is still very limited. My aim is to understand in molecular detail how common sequence elements – upstream open reading frames – engage in the regulation of protein synthesis in order to control and to fine tune protein production and how misregulation results in human disease.

Mitochondria are cellular organelles capable of decoding intracellular signals into markedly different actions, from energy production to cell death. In many instances, these signaling molecules are calcium ions. Mitochondria from virtually all vertebrates are integrated into calcium-dependent signal transduction cascades that regulate neurotransmission, muscle contraction, hormone secretion, and cell proliferation, just to list a few. Although a mitochondrial role in calcium homeostasis has been suggested more than half a century ago, it is still a mystery how the organelle senses, deciphers, and responds to calcium signals. Our laboratory aims at identifying the molecular machines and mechanisms responsible for transmitting information to and from mitochondria and at elucidating their involvement in human diseases. To this goal, we combine large-scale, computational and experimental strategies with focused genetic, biochemical, and physiological studies of mitochondrial functions.