Polymer Concepts Related to Post-translational Modification of Neurodegeneration-Linked RNA-Binding Proteins (R08)

• Subject Area: Biochemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 464588647

The aim of this project is to understand the regulatory impact of post-translational modifications (PTMs) on the neurodegeneration-linked RNA-binding proteins TDP-43 and FUS. In the first funding period, we will focus on known disease-associated PTMs, in particular hyperphosphorylation of TDP-43 and arginine methylation in FUS. We will study how these PTMs affect the proteins’ phase-separation / aggregation behaviour, their structural features and their interactions with negatively charged biopolymers (RNA, ssDNA, poly(ADPribose)). We will also establish a pipeline to identify both physiological and disease-linked PTMs on TDP-43 and FUS using PTM proteomics, e.g. phospho-proteomics.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1551: Polymer Concepts in Cellular Function
• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Project Heads: Professorin Dr. Dorothee Dormann; Professor Dr. Lukas Stelzl