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Archiv-Übersicht     Angebot Nr. 14080

Angebotsdatum: 13. November 2020
Art der Stelle: Doktorarbeit / Diplomarbeit
Fachgebiet: Humanmedizin > Immunologie
Titel des Themas: The NLRP3 inflammasome in response to Staphylococcal toxins and infection

Institut: Interfakultäres Institut für Zellbiologie, Abteilung Immunologie
Adresse:
Frau Ana Tapia Abellán
Auf der Morgenstelle 15
72076 Tübingen
Tel.:    Fax.:
Bundesland: Baden-Württemberg
Homepage:
E-Mail Kontakt: mail

Beschreibung: NLRP3 is a cytosolic sensor of the innate immune system critical for host immune responses against bacterial, fungal, and viral infections. It has also been linked to human inflammatory disorders when dysregulated, including cryopyrin-associated periodic syndromes (CAPS), Alzheimer, diabetes, gout, stroke and atherosclerosis. NLRP3 is able to sense exogenous and endogenous (sterile) insults during infection, tissue damage or cellular stress with the mechanism not clear until the moment. Staphylococcus aureus escapes from macrophages via NLRP3-dependent responses to staphylococcal toxins (e.g. hemolysins and leukocidines) that allow S. aureus to colonize epithelial surfaces, invade host tissues, and evade the immune response, leading to surface and life-threatening systemic infections. Upon activation, NLRP3 oligomerizes and recruits ASC and caspase-1 to form and active NLRP3 inflammasome initiating inflammation (release of mature IL-1β and other alarmins). Unfortunately, the molecular details are not well understood, so our vision is to elucidate how NLRP3 operates during toxin sensing. Addressing this hypothesis would help explain the effects of microbial toxins during the host response and may help devise new anti-infective strategies.
Methoden: Methods and skills to learn | A selection of the following methods established in our lab: Immunology (PBMC preparation, cell culture assays of cell lines and primary human and mouse immune cells, ELISA, flow cytometry), molecular biology (mutagenesis, PCR, restriction digests, sub-cloning), protein biochemistry (SDS-PAGE, immunoblot, immunoprecipitation, chromatography), reporter signaling assays, bioluminescence resonance energy transfer (BRET), tissue analysis (immunofluorescence), data analysis, scientific writing and presentation.
Anfangsdatum: 11. Januar 2020
Geschätzte Dauer: 1 Jahr
Bezahlung: TV-L E13 65%
Papers: Suggested reading:
1. Melehani JH, Duncan JA. Inflammasome activation can mediate tissue-specific pathogenesis or protection in Staphylococcus aureus infection. Curr Top Microbiol Immunol. 2016;
2. Muñoz-Planillo R, Kuffa P, Martínez-Colón G, Smith BL, Rajendiran TM, Núñez G. K+ Efflux Is the Common Trigger of NLRP3 Inflammasome Activation by Bacterial Toxins and Particulate Matter. Immunity. 2013;
3. Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. International Journal of Molecular Sciences. 2019.
4. Tapia-Abellán A, Angosto-Bazarra D, Martínez-Banaclocha H, de Torre-Minguela C, Cerón-Carrasco JP, Pérez-Sánchez H, et al. MCC950 closes the active conformation of NLRP3 to an inactive state. Nat Chem Biol. 2019;


Sonstiges: In order to execute this project and complement our laboratory team, the research section Innate Immunity hopes to recruit an additional excellent and enthusiastic researcher. You would be part of a dynamic research group with a solid track record, and located in an excellent scientific environment, the Department of Immunology at the University of Tübingen, one of Germany’s Excellence Universities. The project is embedded in the DFG-funded Cluster of Excellence “Controlling microbes to fight infection” (CMFI) and represents a collaboration with the labs of Christiane Wolz (Staphylococcus aureus and host interactions) and Thilo Stehle (Structural Biology). In our well-funded laboratory you would find a friendly, well-connected and international environment, and a firm commitment to good supervision and professional development.

Master degree (or equivalent) in biological sciences or medicine, research experience in molecular biology (mutagenesis, PCR, sub-cloning) and some experience in cellular biology, microbiology/virology, protein biochemistry and/or immunology; high motivation to work independently and as part of a team; good command of the English language (written and spoken); both German and international applications encouraged. German skills are not required to apply successfully. Since this is a new project, courage, the ability to find solutions and think independently will be essential.

Funding Notes: Position to start around January 2021 and fully funded for a duration of 1 year. The position may be ideal for German MSc graduates and MS graduates wishing to spend one year abroad in Germany working on an exciting project and learning new techniques. Depending on progress and further funding, the position may be then extendable upon positive evaluation, providing the opportunity for the student to enrol in a PhD. Remuneration is via the German TV-L E13 65% payscale via a regular employment contract with the University Hospital Tübingen.

Your application: Please apply electronically to ana.tapia-abellan@uni-tubingen.de and alexander.weber@uni-tuebingen.de with all of the following: Cover/motivation letter (max 1 A4), CV, transcripts and certificate of MSc and BSc degree, support letter from at least 1 previous supervisor. Applications will be reviewed on an ongoing basis and interviews scheduled accordingly.

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