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  • Bioinformatična analiza podatkov, pridobljenih na mišjem modelu prionske bolezni z metodo RiboTag in vzpostavitev celične linije za njeno vrednotenje = Bioinformatic analysis of RiboTag translatome profiling data from a mouse prion disease model and establishment of a cell line for RiboTag method evaluation : magistrski študijski program Laboratorijska biomedicina
    Koderman, Maruša
    Neurodegenerative diseases are a group of disorders affecting the nervous system that develop as a consequence of protein misfolding and aggregation. These pathological changes affect only specific ... brain areas and the mechanisms behind this regional preference are unknown. Elucidating the strategies employed by different brain cell types in confronting protein aggregates would lead to a better understanding of this phenomenon, known as selective vulnerability. To facilitate this task, several transgenic tools were developed to study cell-type-specific gene regulation in mice. Among the most notable are RiboTag and TRAP (translating ribosome affinity purification), which rely on epitope-tagging of polysomes (translating ribosomes) for the extraction of ribosome-bound mRNA. Combining RiboTag or TRAP with RNA sequencing provides a genome-wide snapshot of the changes occurring in specific cell populations under various conditions. This strategy is particularly suited for studying pathophysiological states which rarely develop as a consequence of a single gene or protein abnormality. Rather, the cellular events resulting in disease can be viewed as a perturbation of an intricate network of interactions between diverse molecular components. Applying the concepts of graph/network theory to molecular interaction networks can contribute to understanding of disease mechanisms, thereby facilitating drug-target prediction and biomarker discovery. In this thesis, we used a network-based approach to study how different brain cell types respond to a prion disease called scrapie, a fatal neurological disorder caused by misfolding of the endogenous prion protein. Prion disease-related communities within cell-type-specific molecular networks (disease modules) were identified using a modified DIAMOnD algorithm in which information on protein interaction patterns was combined with data from a RiboTag-based gene expression study. We show that the modified algorithm can outperform the original version. Moreover, we reveal that astrocytes, GABAergic neurons, and glutamatergic neurons each face ensuing prion disease with unique changes to gene expression. To verify these results in the context of the recently discovered phenomenon of ribosome specialization, we developed a tool for side-by-side comparison of RiboTag and TRAP technologies. Particularly, we established two murine cell lines using CRISPR/Cas9 which allow for an unbiased comparison of mRNA profiles obtained by both methods.
    Vrsta gradiva - magistrsko delo ; neleposlovje za odrasle
    Založništvo in izdelava - Ljubljana : [M. Koderman], 2021
    Jezik - angleški
    COBISS.SI-ID - 92038403

Knjižnica Signatura – lokacija, inventarna št. ... Status izvoda
Fakulteta za farmacijo, Ljubljana Knjižnica
mlab 616 KODERMAN MARUŠA Bioinfor 283
IN: 0017168 		prosto - za čitalnico
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