Postdoc position on neurodegeneration-linked RNA-binding proteins at the Institute of Molecular Biology in Mainz, Germany

Posted on October 28,

The laboratory of Dorothee Dormann at Mainz University and the Institute of Molecular Biology (in Mainz, Germany) is looking for a Postdoctoral Researcher to work on post-translational modifications on neurodegeneration-linked RNA-binding proteins.

Post translational modifications (PTMs) play an important role in modifying protein function and cell physiology, but have also been linked to many diseases, including neurodegenerative disorders. Several proteins that form insoluble aggregates in neurodegeneration patients (e.g. Tau in Alzheimer’s disease, RNA-binding proteins TDP-43 or FUS in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)), are abnormally post-translationally modified. Aberrant PTMs could play an important pathological role in neurodegeneration and contribute to protein mislocalisation, aggregation and/or functional impairment. Alternatively, PTMs may have a protective role and counteract these pathological changes. So far, even though several different PTMs have been detected on TDP-43 and FUS in different proteomic studies, it is largely unclear which PTMs are specific to physiological or pathological conditions, and how these PTMs alter the proteins’ polymer and phase separation behaviour as well as their functional properties in cells.

A variety of different PTMs (e.g. phosphorylation, methylation, acetylation, ubiquitylation and SUMOylation) have been identified on TDP-43 and FUS either in low throughput and proteomic studies (www.phosphosite.org), however this data is a collection from diverse cell and tissue types under different conditions. It is therefore not known which of these PTMs occur under basal conditions and which arise under stress or disease conditions. Moreover, the functional impact of the diverse PTMs of TDP-43 and FUS is largely unclear. In this project, we plan tosystematically identify PTMs on TDP-43 and FUS in neuron-like cells exposed to different stress conditions and in ALS/FTD post-mortem brains, using biochemical purifications and PTM proteomics. Moreover, we seek to investigate the functional impact of diverse PTMs on the proteins’ biophysical properties and phase separation/aggregation behaviour, on their interactions with nucleic acids and RNA regulatory functions, as well as their subcellular localization and transport. To this end, the candidate will have the chance to develop and apply a variety of biophysical, biochemical and cellular techniques to study the functions of post-translational modifications on disease linked RNA-binding proteins.

We are looking for highly curious and open-minded applicants, motivated to develop and drive an ambitious project. Applicants should currently hold a PhD (or be about to complete their doctoral studies) in biochemistry, biology, biophysics or related disciplines. Applicants will have extensive experience with mass spectrometry or biophysical characterization of IDPs. We seek team players with enthusiasm to engage in collaborations and other lab projects.

For more information on the project and requirements, please visit its webpage (www.imb.de/students-postdocs/imb-postdoc-programme/apply-to-the-ippro/apply-to-the-ippro-new/post-translational-modifications-on-neurodegeneration-linked-rna-binding-proteins).

The Institute of Molecular Biology (IMB, www.imb.de) is a centre of basic research on the campus of Mainz University, Germany. Our research focuses on the biology of the nucleus, ranging from the molecular to the organismic level. We are currently recruiting new postdocs that will benefit from the training activities and receive active support for their career development through our IMB Postdoc Programme (IPPro).

If you are interested in this positions, please apply at www.imb.de/postdocs. The deadline for applications is 25 November 2021. For more information, click here.