PhD Scholarships in Molecular Basis of Neurodegeneration, University of Tuebingen, Germany
Two Ph.D. student positions are available in the Research Group Synaptic Plasticity, at the Hertie-Institute for Clinical Brain Research, University of Tuebingen, Germany. Our group addresses the molecular and cellular basis of synaptic plasticity.
Special focus of the advertised project will be
(1) Modeling age-dependent proteotoxicity in adult Drosophila
(2) In vivo imaging of synaptic APP processing
(1) Modeling age-dependent proteotoxicity in adult Drosophila
Many diseases of aging, including Alzheimer’s disease and various forms of Parkinsonism, are associated with proteotoxicity caused by improper folding and aggregation of proteins. Recently a Drosophila “Alzheimer” model was described which allows key stages in disease progression to be studied. Specifically it facilitates analysis of processing of the Alzheimer precursor protein (APP) into the Aß peptide which has been implicated as the main instigator of disease [Greeve et. al, JNS, 2004 p 3899]. We have utilized this model to identify putative modifiers that link aging and APP induced neuronal cell death [unpublished results]. Furthermore, we want to address the effect of modifying signalling pathways involved in aging on the neurodegeneration apparent in this model. Subsequently we will assess the effects of these modifications on neurodegeneration induced by Aß alone [Iijima et. al., PNAS, 2004. p 6623], tau [Wittmann et. al., Science, 2001 p 711] and other neurodegenerative diseases, such as Parkinson’s and spinocerebellar ataxia 3 (SCA3). In addition to fly genetics and husbandry, specific techniques designed to test behavioural changes, memory/learning deficiencies and retinal degeneration have been designed for use in this project. The ideal candidate is a highly motivated student with top grades, talent and creativity who is willing to visit collaborating laboratories in the course of his/her PhD.
(2) In vivo imaging of synaptic APP processing
In this Ph.D. project in vivo imaging [Füger et al., Nature Protocols 2007. p 3285; Rasse et. al., Nature Neuroscience 2005. p 898] and structural analysis [Kittel et. al., Science 2006. p 1051] will be combined to study, in vivo, how soluble fragments of APP-related proteins effect synapse formation, maturation and elimination at the Drosophila neuromuscular junction. The mechanism by which misregulated APP/APPL function leads to pathological events and subsequent symptoms of neurodegeneration will be investigated. Studying this effect in vivo will allow the temporal sequence of cellular events to be deciphered. Investigations shall furthermore clarify the exact cellular localization and functional relevance of APP/APPL processing for synaptic function. The ideal candidate is a highly motivated student with top grades, talent and creativity who is willing to visit collaborating laboratories in the course of his/her PhD.
The two advertised positions are financed by the German Research Center for Neurodegenerative Diseases (DZNE) in Tuebingen and the Graduate Training Center Centre of Neuroscience at the University of Tuebingen, Germany. Highly qualified graduate students are invited to apply for this 2-years scholarship that can be extended to a third year. The scholarships are funded by the German Helmholtz Research Center for Neurodegenerative Diseases. The research findings should eventually translate into novel diagnostic, preventive, and therapeutic strategies.
Contact: Tobias Rasse
tobias.rasse[ at ]uni-tuebingen.de
www.hih-tuebingen.de/synaptic-plasticity/