Prof. Dr. Carmen Nussbaum

Brief research description:
My group studies the cellular and molecular mechanisms of aging and age-related neurodegenerative diseases, such as Alzheimer‘s disease or Parkinson’s disease. We use the model organism Caenorhabditis elegans and human cell culture models to investigate the propagation and intercellular spreading of disease-linked proteins, such as alpha-synuclein and Tau. Our recent studies showed that the intercellular spreading of alpha-synuclein triggers endo-lysosomal rupture in receiving cells (Sandhof et al., Autophagy, 2020). In a genome-wide RNAi screen we have now identified genes that affect lysosomal integrity during aging, which we are currently characterizing (unpublished). In addition, we demonstrated that chaperone-mediated disaggregation of amyloid protein aggregates generates toxic protein species, which might play a role in the progression of neurodegenerative diseases (Tittelmeier et al., EMBO J, 2020; Nachman et al., JBC, 2020; Tittelmeier et al., Commun Biol, 2022). Furthermore, we have established cell-type specific ribosome profiling in C. elegans to identify cell type specific factors involved in spreading and selective vulnerability (unpublished).

Research methods:
Our methods range from confocal microscopy, genetics (e.g. CRISPR), cell biology and biochemistry to systems analysis (using ribosome profiling), mainly in C. elegans, but also in mammalian cell culture. The nematode is easily genetically manipulated and its transparency allows observation of the intercellular spreading of fluorescently labeled disease proteins in an intact living organism. Moreover, its short and defined lifespan facilitates studying the impact of aging on cellular protein homeostasis and neurodegeneration.

Website: http://www.nussbaumlab.com