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Archiv-Übersicht     Angebot Nr. 14781

Angebotsdatum: 13. Januar 2023
Art der Stelle: Diplomarbeit
Fachgebiet: Chemie > Biochemie
Titel des Themas: TRMT2A as PolyQ disease modifier

Institut: Institute of Structural Biology
Herr David Settele
Ingolstädter Landstraße 1
85764 München
Tel.:    Fax.:
Bundesland: Bayern
Homepage: http://https://www.helmholtz-munich.de/en/stb/research-groups/niessing-lab
E-Mail Kontakt: mail

Beschreibung: The tRNA methyltransferase 2 homolog A (TRMT2A) is the dedicated enzyme for methylation of uridine 54 in transfer-RNA (tRNA). Human TRMT2A has also been described as modifier of poly-glutamine- (polyQ-) derived neuronal toxicity.
Corresponding human polyQ pathologies include Huntington’s disease and constitute a family of devastating neurodegenerative diseases. A polyQ tract in the corresponding disease-linked protein causes neuronal death and symptoms like impaired motor function, as well as cognitive impairment.
PolyQ diseases usually leads to death 10 – 20 years after the first symptoms. Currently, there is no cure for PolyQ disease, only symptomatic treatment can be performed.
In polyQ-disease models, silencing of TRMT2A reduced polyQ-associated cell death and polyQ-protein aggregation, suggesting this protein to be a valid drug target against this class of disorders.
We at the Institute of Structural Biology at the Helmholtz Center Munich study the structure and function of the TRMT2A protein. Our overall goal is to find a specific inhibitor for TRMT2A. Which may be taken as prophylaxis by people with PolyQ disease to slow down the progression of the disease. For this goal, it is particularly important to better understand TRMT2A structurally so that specific inhibitors can be designed. Until now there is no complete experimental structure but we want to change this! Using X-ray crystallography, we want to resolve the structure of TRMT2A. Besides the structural aspect, we also want to better understand TRMT2A on a molecular and cellular level. High-throughput techniques have already uncovered potential interactions and pathways in which TRMT2A plays a role. We are currently trying to validate these data to gain a better understanding of what roles TRMT2A has besides methylation of RNA.
Interested? Join us on this crucial and challenging task for your master thesis or contact us if you want to be part of this as an intern.
Methoden: • Molecular cloning
• Protein expression & purification
• Protein crystallization
• RNA biochemistry
• Surface plasmon resonance measurements
• Proteome interaction studies
• Enzymatic assays
• Cell culture
• Interpreting and evaluating results
• Independent lab work
Anfangsdatum: 13. Februar 2023
Geschätzte Dauer: 6 months
Papers: - Michael A Margreiter, Monika Witzenberger, Yasmine Wasser, Elena Davydova, Robert Janowski, Jonas Metz, Pardes Habib, Sabri E.M. Sahnoun, Carina Sobisch, Benedetta Poma, Oscar Palomino-Hernandez, Mirko Wagner, Thomas Carell, N. Jon Shah, Jörg B. Schulz, Dierk Niessing, Aaron Voigt, Giulia Rossetti,
Small-molecule modulators of TRMT2A decrease PolyQ aggregation and PolyQ-induced cell death,
Computational and Structural Biotechnology Journal,
2022, https://doi.org/10.1016/j.csbj.2021.12.029.

- Monika Witzenberger, Sandra Burczyk, Luisa M. Welp, Mirko Wagner, Thomas Monecke, Robert Janowski, Thomas Carell, Henning Urlaub, Stefanie M. Hauck, Aaron Voigt, Dierk Niessing,
Human TRMT2A methylates different components of the translation machinery and contributes to translation fidelity, 2022 (in press.)