Elucidating the (dys)function and regulation of TAF15 in neuronal RNA metabolism in ALS/FTD

• Applicant: Dr. Henrick Riemenschneider
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Molecular Biology and Physiology of Neurons and Glial Cells ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572312326

I propose defining the role of TAF15, an RNA-binding protein recently discovered to form disease-typifying amyloid fibrils in neurodegeneration, in neuronal metabolism under both healthy and diseased conditions. I will study TAF15's ill-defined RNA processing functions in cortical and motor neurons, cell types selectively affected in the devastating, fast-progressing disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Using innovative sequencing methods in human induced pluripotent stem cell (hiPSC)-derived neurons, I will reveal changes in gene expression and uncover RNA mis-processing events upon TAF15 dysfunction. I will also identify genetic factors influencing TAF15's regulatory repertoire and link TAF15 self-assembly (condensation) to its functionality. These findings will deepen our mechanistic understanding of how RNA-binding proteins (dys)function in health and disease, and may provide novel therapeutic strategies for combating ALS/FTD.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Aaron D. Gitler, Ph.D.