The Institute of Clinical Neurobiology at Würzburg University Hospital has a vacancy for a PhD student (neurobiology with a focus on cell biology) to start as soon as possible. The project is entitled "Design and Development of Therapeutic Strategies against Motoneuron Disorders." Our research focuses on the identification of cellular targets to bypass affected signaling pathways in spinal muscular atrophy with respiratory distress type 1 (SMARD1). The project is financed by the Deutsche Forschungsgemeinschaft and the foundation SmashSMARD, Germany. Identification and characterization of cellular target molecules with compensatory potential to bypass affected signaling pathways in SMARD1, using iPSCs from SMARD1 patients as well as relevant animal models. Detailed analysis of the helicase IGHMBP2 (ribosome-associated ATPase/helicase, affected in SMARD1) and its role in motoneuron degeneration. Studies on SMARD1 mouse models with focus on defective microcircuits for movement patterns. As part of the project funded by the German Research Foundation (DFG), cellular target molecules will be identified that can compensate for affected signaling pathways in spinal muscular atrophy with respiratory insufficiency (SMARD1). To this end, iPSCs and primary motoneurons of SMARD1 mouse models will be used. A detailed analysis of the helicase IGHMBP2 (ribosome-associated ATPase/helicase, affected in SMARD1 patients) is planned, as well as the extent to which its loss leads to motoneuron degeneration in the spinal cord. The cell culture work is supplemented by studies on mouse models to investigate defective communication pathways between motoneurons, sensory neurons, and non-neuronal cells. These studies serve to elucidate cell-autonomous and non-cell-autonomous disease mechanisms that ultimately lead to motoneuron loss. Further information can be found in: Jablonka et al., Biomedicines 2024 Apr 11;12(4): 845. doi: 10.3390/biomedicines12040845 Surrey et al., Neuroscience. 2018 Aug 21; 386: 24-40. doi: 10.1016/j.neuroscience.2018.06.019 Krieger et al., Brain. 2014 May; 137(Pt 5): 1374-93. doi: 10.1093/brain/awu059 Krieger et al., Neurobiology of Diseases 2013 Jun; 54: 169-82. doi: 10.1016/j.nbd.2012.12.010 We are looking for a highly motivated PhD student with basic knowledge in neurobiology and good technical background in molecular biology (qRT PCR, Western Blots, cloning and cell culture techniques). The candidate will use advanced molecular biology and cell culture techniques including life cell imaging, iPSC techniques and culturing of primary mouse motoneurons for studying alterations in diseased neurons. Motor function studies, histological analysis of mouse tissue and confocal microscopy will complete the project. The PhD student will be supported by technical assistance. The project profits from strong national and international cooperations and knowledge transfer between partner groups, and is well embedded in the research focus of the institute. He/she will have access to a modern and well-equipped research facility. The institute boasts above-average equipment for confocal microscopy, an excellently managed animal facility, and cell culture laboratories equipped for both human stem cell cultures and the production of lentiviral vectors and adeno-associated viruses (AAVs).