Jobs

Postdoc, Post-Translational Modifications on RNA-Binding Proteins

Employer

Johannes Gutenberg University

Location

Mainz, Germany

Principal Investigator

Dorothee Dormann

Contact

Applications via this link until Nov 25, 2021: https://www.imb.de/students-postdocs/imb-postdoc-programme/apply-to-the-ippro.

Description

The Dormann lab at JGU and IMB Mainz seeks a postdoctoral fellow to study post-translational modifications on neurodegeneration-linked RNA-binding proteins.

Scientific Background

Post-translational modifications (PTMs) play an important role in modifying protein function and cell physiology, but also have been linked to many diseases, including neurodegenerative disorders. Several proteins that form insoluble aggregates in neurodegeneration patients, e.g., Tau in Alzheimer’s disease and the 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 mislocalization, 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 behavior as well as their functional properties in cells.

The Project

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 (see 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 to systematically identify PTMs on TDP-43 and FUS in neuron-like cells exposed to different stress conditions and in ALS/FTD postmortem 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 behavior, 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.

Requirements

  • Ph.D. in biochemistry, biology, biophysics, or related discipline.
  • Extensive experience with mass spectrometry or biophysical characterization of IDPs.
  • Team player with enthusiasm to engage in collaborations and other lab projects.
  • Highly curious and open-minded, motivated to develop and drive an ambitious project.