Gist als modelorganisme om de structurele eigenschappen van het ziektegerelateerd eiwit Tau te onderzoeken
Year: 2023
Type: dissertation
Abstract: Neurodegenerative disorders associated with the profuse and aberrant accumulation of the hyperphosphorylated microtubule-associated protein Tau are better known as Tauopathies. This group of diseases imposes a major impact on the cognitive and physical abilities of the patients and inevitably lead to mortality. Due to the continuously growing aging population and the lack of any disease-modifying drug that can stop or reverse the witnessed cognitive deterioration, our society will have to deal with enormous numbers of affected individuals that will inflict a major socio-economic burden. Despite a tremendous amount of research, disease mechanisms and pathogenesis still remain elusive due to the substantial heterogeneity in clinical, genetical and biochemical presentation. Different model organisms, such as Drosophila melanogaster, Caenorhabditis elegans and transgenic rodent models, and unicellular organisms, including human cell lines and yeast, are extensively used by the research community to unravel the molecular machinery responsible for the onset and progression of these diseases. Yeast is often preferred as a model system because of its genetical and environmental flexibility and its short generation time. In addition, a huge share of yeast genes are known to have mammalian orthologues or share significant domain similarity. These traits prompted the use of this organism to untangle and understand various human diseases, such as cancer and different neurodegenerative disorders. Throughout this doctoral thesis, the budding yeast Saccharomyces cerevisiae has been the model organism of choice for two research chapters concerning the microtubule-associated protein Tau. The first research line of this PhD describes the use of a humanized S. cerevisiae model for the production of human Tau and the subsequent generation of novel monoclonal Tau antibodies. The second research line describes the construction and further validation of the newly generated chimeric protein Ure2::K18 using a yeast-based aggregation and prion detection assay to examine the intrinsic oligomerization and prion-like properties of the microtubule-binding repeat domain of Tau.
Source: Lirias (KU Leuven)
Author: Verelst, Joke
Institution: KU Leuven
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6982042600