CELLULAR HOMEOSTASIS AND ADAPTATION TO STRESS
All living cells have to maintain their homeostasis in the light of myriads of life threatening stresses. Those can come from outside the cell (extrinsic) or generate within the cell (intrinsic). An insufficient adaptation to the stress finally causes organelle dysfunction and apoptotic cell death, which is linked to disease and neurodegeneration. Our principle interest is to discover the molecular events that adjust cellular functions upon different chemical and environmental challenges in order to survive and proliferate. We mainly use for our studies a simple, unicellular model organism, baker´s yeast (Saccharomyces cerevisiae), and we apply genetic, genomic, biochemical, confocal microscopy and single cell approaches to gain novel insights into the principles of stress adaptation. We currently focus at the following specific research topics:
Homeostasis of mitochondria and other organelles in apoptosis
Mitochondria are highly dynamic organelles of eukaryotic cells and play a crucial role in the induction or suppression of programmed cell death. We study the mechanisms, which control the balance between pro-apoptotic death and anti-apoptotic survival in the yeast model. Central regulators here are bioactive lipid species derived from sphingolipid metabolism. They act as strong apoptotic inducers at the endoplasmic reticulum/mitochondria interface. We use transcriptomic, functional genomics, fluorescent microscopy and biochemical approaches to elucidate evolutionarily conserved pro- and anti-apoptotic regulatory mechanisms. Specifically, we are investigating how pro-apoptotic lipids act through mitochondrial protein import, protein aggregation, autophagic pathways and other cellular functions.
Dynamic control of gene expression in real time
Our lab has developed non-invasive gene expression reporters based on destabilized luciferases, which permit the time resolved quantification of gene regulation in the living yeast cell. This technology is applied by us to understand the full dynamic range of cellular adaptation and how it changes by the genetic, physiological and environmental background of the cell. We are especially interested in the transcriptional responses to chemicals including antifungal drugs.
Altered gene expression during aging and evolution
The efficiency of activating gene expression upon stress is not constant throughout the cells´ life. The decline of accurately responding to environmental insults might be in fact an important feature of aging cells. We are investigating this phenomenon in the yeast model by the combination of cell separation at determined ages and flow cytometric quantification of the stress response via fuorescent reporters. We are additionally interested in how transcriptional stress responses change during evolution to adapt to specific environmental niches. To this end, we make use of different natural S. cerevisiae isolates and evolutionarily related yeast species. We capture different stress behaviors with quantitative live-cell reporters in order to genetically identify how specific and divergent stress behaviors are created during evolution.