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Archiv-Übersicht     Angebot Nr. 13052

Angebotsdatum: 19. September 2018
Art der Stelle: Doktorarbeit
Fachgebiet: Humanmedizin > Physiologie
Titel des Themas: Targeting Müller cells for complement modulating gene addition therapy in a mouse model for Stargardt disease type 1

Institut: Institute of Physiological Genomics
Frau Prof. Dr. rer. nat. Antje Grosche
Großharderner Str. 9
82152 Planegg-Martinsried (Munich)
Tel.:    Fax.:
Homepage: http://https://www.genom.physiol.med.uni-muenchen.de/research_gr/grosche_group/index.html
E-Mail Kontakt: mail

Beschreibung: The research group “Molecular Neurophysiology" at the Institute of Physiological Genomics (Ludwig-Maximilians-University of Munich) offers at the earliest possible date, but latest at 1st January 2019, a position as PhD student. The position is initially funded for 36 months by the DFG and is available from November 2018 (pay scale 65% E13 TV-L)

We are a highly motivated research group dedicating our work to investigations how the neuroprotective potential of the major macroglial cell of the retina, the Müller cell, can be enhanced under disease conditions aiming to develop treatment options for complex retinal degeneration. We define ourselves by high scientific standards as well as a strong relation to translational approaches.

The retina is an immune privileged tissue, where the complement system (CS) is tightly con­trolled. Lipofuscin accumulation in Stargardt disease causes local CS activation and results in parainflammation. Important players modulating the retinal immune response are Müller cells, retinal glia that are in contact with all other retinal cell types. To balance the activity of the immune system could be an important therapeutic strategy for retinal degeneration and holds promise in various clinical trials using therapeutic antibodies targeting main factors of the CS. In the present project, we aim to compare the local role and modulation of the CS in mouse models for inherited and acute retinal degeneration and on basis of this knowledge, we seek to develop a gene therapeutic approach targeting Müller glia to modulate the retinal complement homeostasis in the context of retinal disease in the project “Targeting Müller cells for complement modulating gene addition therapy in a mouse model for Stargardt disease type 1”, which is funded by the German Research Organization (DFG). We will closely collaborate with Dr. Diana Pauly at the Eye Clinics of the University Hospital of the University of Regensburg and other members of the DFG priority program SPP2127.

Activities and responsibilities:
Experience in basic cell molecular and biochemical techniques (e.g. Western blotting, immunoprecipitations, gene expression analysis, cloning, cell culture, AAV- or lentiviral transductions, microscopy etc.) would be beneficial.

Qualification profile:
Applicants should be highly motivated and committed to basic science with great interest in retinal diseases and the ability to conduct independent research. The PhD position requires a master´s degree/diploma in life sciences or related disciplines.
Methoden: A highly dedicated, stimulating, diverse and international team in an exceptionally collaborative environment at the BioMedical Center of the LMU in Plannegg-Martinsried

Use of state of the art equipment (AAV facility, various excellent core facilities at the BioMedical Center, e.g. STED microscopy, proteomics, bioinformatics, FACS, various sequencing platforms)

An exciting and highly translational research field

Highly innovative projects within the field of retinal research

Presentation and publication of the data at international scientific meetings and in journals
Anfangsdatum: 19. September 2018
Geschätzte Dauer: At least 3 years
Bezahlung: Pay scale 65% E13 TV-L
Papers: Pauly D, Schäfer S, Grassmann F, Pfaller AM, Straub T, Weber BHF, Hauck SM, Grosche A. Cell type-specific complement expression from healthy and diseased retinae. BioRxiv: 413088.

Wagner L, Pannicke T, Rupprecht V, Frommherz I, Volz C, Illes P, Hirrlinger J, Jägle H, Egger V, Haydon PG, Pfrieger FW, Grosche A. Suppression of SNARE-dependent exocytosis in retinal glial cells and its effect on ischemia-induced neurodegeneration. Glia. 2017 Apr, 65:1059-1071.

Schäfer N, Grosche A, Schmitt SI, Braunger BM, Pauly D. Complement Components Showed a Time-Dependent Local Expression Pattern in Constant and Acute White Light-Induced Photoreceptor Damage. Front Mol Neurosci. 2017 Jun, 10:197.

Grosche A, Hauser A, Lepper MF, Mayo R, von Toerne C, Merl-Pham J, Hauck SM*. 2016. The proteome of native adult Muller glial cells from murine retina. Mol Cell Proteomics. 2016 Feb, 15:462-480.

Schäfer N, Grosche A, Reinders J, Hauck SM, Pouw RB, Kuijpers TW, Wouters D, Ehrenstein B, Enzmann V, Zipfel PF, Skerka C, Pauly D. Complement Regulator FHR-3 Is Elevated either Locally or Systemically in a Selection of Autoimmune Diseases. Front Immunol. 2016 Nov, 7:542.
Sonstiges: Please include a CV, brief summary of your previous work experience, a short letter of motivation, copies of university degree(s) with academic records, and two reference letters (or the referee’s contact info).

Applications by October 31, 2018 to Prof. Dr. Antje Grosche via mail: Antje.Grosche(at)med.uni-muenchen.de