The project is focused on the identification of DUBs affecting the huntingtin and/or ataxin 3 ubiquitination status. Initial studies will focus on the characterization of the DUB landscape in a cellular model of PolyQ disease. This will be followed by specific techniques aiming to identify DUBs affecting clearance, subcellular localization and, where possible, function of the underlying PolyQ protein. The described studies will mainly be performed at the Dept. of Neurodegeneration at H. Lundbeck A/S as part of the EU funded consortium “TreatPolyQ”.
This network consists of 14 partners throughout Europe and is the combination of experts from basic and translational research from both industry and academia. The applicant will spend part of the program in the lab of one of the other partners and will have access to courses covering aspects of structural biology, protein degradation, model organisms and drug development.
Polyglutamine diseases are a group of inherited neurodegenerative disorders characterized by an expansion of a polyglutamine tract within specific proteins. The two main members of this disease family are Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3) with the affected proteins being huntingtin and ataxin 3 respectively. One of the hallmarks of polyQ diseases is the accumulation/aggregation of the expanded polyQ protein in selected cellular compartments. Alterations in the cellular turn-over, subcellular localization and protein function of huntingtin and ataxin 3 have been described as important characteristics associated with disease. The three features are, among other, regulated by posttranslational modification through the attachment of ubiquitin (Ub) residues. The ubiquitination status defined by the number of residues attached, whether these Ub’s are assembled in a straight or branched chain or their respective linkage may thus be key factors involved in disease. Enzymes regulating this ubiquitination status are ubiquitin E3 ligases (E3s) and deubiquitinating enzymes (DUBs) and may thus both represent promising future target classes for HD and SCA3.
• You are highly motivated and enjoy thinking about intricate cellular mechanisms
• You hold a master degree in Biochemistry, Molecular Biology or related
• You have a basic understanding of intracellular mechanisms central for regulating protein catabolic processes (e.g. regulation of ubiquitination, the proteasomal system and autophagy).
• You have documented experience in cell culture; additional experience in Neuroscience will be regarded as an advantage
• You have excellent communication and presentation skills
• You are used to work in multi-disciplinary environments
• You fulfil the formal criteria for applying for this position
a) You are an early stage researcher, meaning that you have not yet been awarded the doctorate degree and are in the first 4 years of your research career
b) At the time of recruitment, you have not resided or carried out your main activity (work, studies etc.) in Denmark for more than 12 months over the past 3 years
The project will be available at the Dept. of Neurodegeneration, H. Lundbeck A/S Ottilavej 9, 2500, Valby, DK in close collaboration with other partners within the “TreatPolyQ” network and the University of Copenhagen (where the successful applicant will be enrolled). Main supervision will be carried out by Justus Dächsel and Karina Fog (H. Lundbeck A/S). For additional information contact Justus Dächsel (Tel. +45 36 43 5101, E-mail: firstname.lastname@example.org).
Source: European Commission EURAXESS