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Dissertation
Investigation of the functional synergy and involvement of different tRNA modifications in translational control
(2020-07-02)
Transfer RNAs are essential adapter molecules employed in the translational process and are highly modified all over their structure. Specific modification of the four canonical ribonucleotides (A, U, C, G) is accomplished by various proteins and/or protein complexes, ranging from simple isomerisations (e.g. Ψ) and methylations (e.g. m5C) up to complex chemical structures (e.g. mcm5s2U, ct6A). The functions of tRNA modifications are linked to the specific position and may influence translation by supporting the native ...
Dissertation
The tRNA binding protein Kti12 and its role in the regulation of Elongator complex
(2020-06-08)
[Summary] Kti12 is a conserved eukaryotic protein showing sequence homology to O-phosphoseryltRNA kinase (Pstk), which is required for the synthesis of selenocysteine tRNA. Saccharomyces cerevisiae Kti12 was originally discovered in a genetic screening for resistance against zymocin, a protein toxin produced by Kluyveromyces lactis. The cytotoxicity of zymocin lies in its anticodon nuclease activity, causing tRNA depletion and cell death in sensitive yeast cells. It recognizes and cleaves a particular wobble uridine ...
Dissertation
Die Physiologie des Wirts-Parasitsystems pathogener Pilze des Eschentriebsterbens
(2019)
In der vorliegenden Arbeit wurde versucht, die optimalen Wachstumsbedingungen des Pilzes H. fraxineus (Haupterreger des Eschentriebsterbens) zu ermitteln. Dafür wurden drei Wachstumsversuche (Nährmedium, pH-Wert und Temperatur) an 25 Pilzstämmen durchgeführt.
• Die Ergebnisse des Nährmediumwachstumsversuches zeigten, dass Maismehl Agar Medium (MmA) die schnellste Kultivierung des Pilzes förderte und als das optimale Nährmedium gelten kann (im Vergleich mit den anderen sechs geprüften Nährmedien).
• Der pH-Wert-Versuch ...
Dissertation
Association of neighboring β-Strands to form the β-barrel structure of the voltage-dependent anion channel, human isoform 1 (hVDAC1) precedes membrane insertion and is largely driven by polar interactions between basic and acidic amino acid side-chains
(2020)
To date, all biophysical folding studies on β-barrel membrane proteins from outer membranes (OMPs) indicated a coupled mechanism of folding and membrane insertion. Most of these studies were performed with smaller OMPs from bacteria. Here we have investigated folding and insertion of a mitochondrial OMP, the voltage-dependent anion-selective channel (VDAC), human isoform 1 (hVDAC1). To examine whether folding and insertion are coupled for hVDAC1, the association of neighboring β-strands of the 19-stranded β-barrel ...
Dissertation
BamB facilitates folding of outer membrane protein A (OmpA) via interactions of its β-propeller with the membrane surface and via a conformation change induced by phosphatidylglycerol
(2019-10-17)
A sufficient folding and insertion of OMPs into the OM of Gram-negative bacteria requires the conserved β-barrel assembly machinery (BAM) complex. The present thesis concerns the structural properties and folding behavior of the lipoprotein BamB and describes its relevance in the synchronized mechanism of membrane insertion and folding of the β-barrel protein OmpA. Furthermore, specific binding sites in BamB involved in the interaction to the lipid membrane or the periplasmic domain of BamA (PD-BamA) were identified ...
Dissertation
Mechanistic Insights into the intrinsic Kinase Regulation of LRRK2
(2019-06)
Obwohl Morbus Parkinson (PD) die zweithäufigste neurodegenerative Erkrankung darstellt, ist der Pathomechanismus kaum verstanden. Es ist jedoch erwiesen, dass PD assoziierte Mutationen die Aktivität der Leucine rich repeat kinase 2 (LRRK2) beeinflussen, sodass diese ein potentielles Drug Target darstellt. Für ein besseres Verständnis wurden daher der intrinsische regulatorische Mechanismus und der Einfluss von Mutationen auf LRRK2 untersucht. Zusätzlich wurde der Einfluss von Nanobodies gegen die ROC Domäne von LRRK2 ...
Dissertation
Translationskontrolle in der Spermatogenese von Drosophila: Charakterisierung eines regulatorischen mRNP-Komplexes
(2012-05-23)
Während der Spermatogenese von Drosophila werden viele mRNAs zwar vor der Meiose transkribiert, dann aber durch Komplexbildung mit Proteinen stillgelegt und erst am Ende der Spermienentwicklung durch Veränderung desselben für die Translation freigegeben. Ein Beispiel hierfür ist die Mst87F mRNA. Während das cis-agierende Sequenzelement in der RNA seit langem bekannt ist, gestaltete sich die Suche nach den trans-agierenden RNA-bindenden Proteinen schwierig. In meiner Diplomarbeit (Stinski, 2007) waren mithilfe von ...
Dissertation
The role of Ken&Barbie in JAK/STAT signalling during development of Drosophila melanogaster
(2005-02-02)
Cell-cell interactions during embryonic development are crucial in the co-ordination of growth, differentiation and maintenance of many different cell types. To achieve this co-ordination each cell must properly translate signals received from neighbouring cells, into spatially and temporally appropriate developmental responses. A surprisingly limited number of signal pathways are responsible for the differentiation of enormous variety of cell types. As a result, pathways are frequently 'reused' during development. ...
Dissertation
Characterization of the role of Drosophila JAK/STAT signalling in cellular proliferation
(2006-01-10)
Der Janus Kinase / signal transducer and activator of transcription (JAK/STAT) Signal- transduktionsweg wird für viele Entwicklungsvorgänge benötigt und spielt eine zentrale Rolle bei der Hämatopoese und bei der Immunantwort. Obwohl der JAK/STAT-Signalweg in den vergangenen Jahren Gegenstand intensiver Forschung war, erschwert die Redundanz des Signalwegs bei Wirbeltieren genetische Untersuchungen zur Identifizierung derjenigen Mechanismen, die den JAK/STAT-Signalweg regulieren. Der JAK/STAT-Signaltransduktionsweg ...
Dissertation
Studies of cap-independent mRNA translation in Drosophila melanogaster
(2005-02-02)
Control of protein synthesis is a key step in the regulation of gene expression during apoptosis and the heat shock response. Under such conditions, cap-dependent translation is impaired and Internal Ribosome Entry Site (IRES)-dependent translation plays a major role in mammalian cells. Although the role of IRES-dependent translation during apoptosis has been mainly studied in mammals, its role in the translation of Drosophila apoptotic genes has not been yet studied. The observation that the Drosophila mutant embryos ...