The Laboratory of Functional Neurogenetics, Hertie Institute for Clinical Brain Research offers Diploma / Masters thesis projects. Research topics of these experimental biology studies are in the field of molecular genetics of age-related neurodegenerative proteinopathies, with particular emphasis on Parkinson's disease:
The neuropathological hallmark of Parkinson's and related diseases are so-called Lewy bodies, which are largely composed of misfolded α-synuclein protein. Neurons have evolved complex cellular and molecular defense mechanisms against such unfolded protein stress. Intracellular transport of misfolded proteins to compartments with high local refolding and degradation capacity (aggresomes, proteasomes, autophagosomes) is particularly important for the large projecting neurons. We investigate the microtubular transport machinery that mediates retrograde axonal transport of the synaptic protein α-synuclein in transfected cell lines, virally transduced primary neuron cultures, the nematode worm Caenorhabditits elegans and transgenic mice, with particular emphasis on histone deacetylases and sirtuins.
Methods include C. elegans culture and genetics, live fluorescence imaging and advanced microscopy, molecular cloning, cell transfection and culture, RNA silencing and molecular pharmacology, protein analysis and enzyme assays.
Impairments of cellular protein degradation systems (proteasome, lysosome/autophagosome) contribute to the pathology of neurodegenerative diseases. We investigate the ubiquitin ligase parkin, the most common gene mutated in familial PD, as well as the seven-in-absentia homolog-1 and dorfin, two enzymes of the same class involved in PD. Cooperative actions of these enzymes with respect to ligation of ubiquitin and related modifiers are studied in cell-free assays, transfected cell lines, and C. elegans. We wish to understand the molecular mechanisms of aggregation-prone protein catabolism.
Methods include molecular cloning, recombinant protein production, yeast 2-hybrid technology, cell transfection and culture, immunoprecipitation / immunoblotting, and enzyme assays.