In the field of Ciliary protein function: roles in DNA damage repair and gene regulation the research group of Prof. Uwe Wolfrum offers the following PhD project:

The role of Usher syndrome protein networks in DNA damage repair and gene regulation

Description: 
Over more than ten years we have successfully identified molecules of the protein interactome related to Usher syndrome (USH) and comprehensively analyzed the USH protein networks that are associated with periciliary membrane adhesion complexes and ciliary transport modules. In the proposed project we will further elucidate the molecular links of USH to gene regulation and DDR. For this we will focus on the two scaffold proteins, namely harmonin (USH1c) and sans (USH1g) and aGPCR GPR98/VLGR1 (USH2c). Preliminary data indicating nuclear translocation of USH proteins and their interaction with gene regulation and DDR signaling certainly supports a role of USH proteins in the machineries of gene regulation and DDR.

In this project we will validate and specify the triggers for the translocation into the nucleus of USH proteins, testing e.g. UV-irradiation, cellular stressors, and phosphorylation conditions. We will comprehensively analyse the nuclear localisation of USH proteins applying high resolution fluorescence and electron microscopy. We will test the influence of gene knockdowns and USH-causing mutations on DDR activation and compare the ciliary and DDR phenotypes. Furthermore, we will monitor the complex partners of the USHproteins in subcellular fractions by targeting the three USH proteins in comprehensive tandem affinity purifications (SF-TAPs) and subsequent MASS-spec analysis. In additional sets of experiments we will identify downstream target genes of the USH protein signaling, analysing transcriptomes before and after protein translocation into the nucleus.

We expect results that will provide novel insights into the pathogenesis of the USH disease and the molecular machineries associated with DDR signalling and the gene regulation sensed by cilia..

We offer:
• The possibility to work on a cutting-edge project using state-of-the-art technology in a highly motivated research team
• A stimulating, diverse and international research environment
• Advanced training opportunities
• A competitive stipend

Required qualifications:
• Master or Diploma
• Motivation to solve complex biological problems
• Excellent communication skills

Starting date: 1 March 2014 or later
Duration of stipend: 3 years, with the possibility of extension
Deadline for applications (exclusively online via web form): 25 November 2013

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