Splicing fidelity dynamics and its proteomic consequences in the aging mouse brain

• Applicant: Nisha Hemandhar Kumar, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Bioinformatics and Theoretical Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 577910116

The central question of this project is: How does splicing fidelity affect the overall flow of information from the transcriptome to the proteome, and what are the physiological consequences for the aging mouse brain resulting from that? This question includes accomplishing the following aims: (1) Quantify age- and sex-related changes in mRNA production (including RNA Pol-II speed, mRNA kinetics and the mRNA isoform-level changes resulting from that). (2) Quantify changes in the translatome and link those changes back to transcript-level changes detected for aim (1). (3) Quantify age- and sex-related protein level and protein state changes from the same brain samples and identify protein-level changes that can be explained by RNA-level and translatome changes observed for aims (1-2). (4) Identify cellular functions and molecular pathways that are particularly affected by those alterations and confirm their physiological consequences using in-vitro cell culture assays.

• DFG Programme: Position