The Allen Frontiers Group funds an exciting opportunity for a postdoctoral position in the Clausen Lab, studying the impact of disease mutations on “Protein Lifespan”. In this project, we will monitor the fate of muscle proteins in cellular and organismal context, focusing on myosin and its life cycle in the native muscle cell environment.
We have pioneered a unique protein-folding reporter to track the fate of muscle myosin in cells. Using C. elegans as primary model organism, we now want to explore the impact of patient-derived myosin mutations at the molecular, cellular and organismal level. We can - for the first time ever - perform genome-wide screens to identify cellular factors and pathways counteracting myosin misfolding and aggregation in muscle cells. The project is supported by a substantial body of unpublished data and can be started immediately. Key objectives include:
- Using patient-derived myosin mutations to study how premature protein misfolding affects muscle function and organismal health.
- Performing targeted, genome-wide screens to identify factors that counteract myosin misfolding and aggregation in muscle tissue.
- Systematic analyses of proteostasis networks in young and old nematodes.
- Mechanistic analysis of factors maintaining myosin homeostasis, thus obtaining critical insights to develop treatments against human muscle diseases.
Just like human beings, a protein's lifespan depends on its primary constitution, education, neighborhood, and environmental factors. Similarly, healthy ageing of a protein is important to avoid premature misfolding and aggregation, associated with severe proteinopathies, such as Alzheimer’s disease or certain myopathies. The lifespan of a protein can be defined as the time from when a newly synthesized polypeptide chain starts to fold, through the assembly into larger protein complexes, to when the protein is degraded, often after it has lost function. While individual steps have been extensively studied in test-tube experiments, we know little about how they are coordinated in complex living animals. For example, why do some proteins live are maintained for a long period of time whereas others turn over rapidly? What cell conditions affect their folding and degradation? Currently, it is not possible to track the entire lifespan of a protein in a living animal due to the lack of reporting tools that cover the folding and maturation stages. To overcome this bottleneck, our group pioneered a special fluorescent reporter to monitor the maturation, ageing and degradation of the muscle protein myosin, enabling us to directly watch the life of myosin in cells and in animals.
About the Lab and the position:
We are a multidisciplinary team, interested in the molecular mechanisms that regulate proteostasis and its influence on protein misfolding diseases and ageing. The used methodology spans biochemistry, proteomics, protein engineering, cell biology, and structural biology. Having pioneered molecular tools to study myosin lifecycle in cultured cells, we have formed a dedicated “C. elegans proteostasis” research focus, for which we now search a postdoctoral leader. Aside from preparing candidates for the next step in their career, the position provides ample opportunity to learn diverse methodologies in mechanistic cell biology, mentioned above, and applying these to study proteostasis networks in C. elegans. Located at the Research Institute of Molecular Pathology, IMP (https://www.imp.ac.at/), a leading international research institute in one of the world’s best cities, Vienna, our lab has access to cutting-edge service facilities (https://www.imp.ac.at/research/services) and benefits from the excellent research community at the Vienna Biocenter Campus (https://www.viennabiocenter.org/). Last not least, our group is part of the vibrant “Ubiquitin and Friends” community in Vienna, https://www.protein-degradation.org/, as well as being in close contact to local groups with expertise in diverse model systems and next-generation screening and genomics approaches.
Qualifications for the position:
- Strong track-record in C. elegans genetics and molecular biology.
- Documented knowledge in at least one of the following topics: proteomics, fluorescence microscopy, chemical biology, structural biology.
- General interest in studying proteinopathies and being a good teamplayer.
- Freedom to explore high-risk concepts, within a three-year fully funded position.
- Access to cutting-edge and state-of-the-art service resources at the IMP and VBC.
- Open, collaborative and interdisciplinary research environment
- Scientific integrity and leadership training, as well as career development support.
- Child-care facilities are available on campus.
How to apply
All applications and supporting materials (letter of motivation, curriculum vitae, list of publications, description of research experience and interests, and two letters of reference) should be submitted to tim.clausen[at]imp.ac.at
Interviews will be held on a rolling basis. As soon as a suitable candidate is found, the position will be filled.