Subsequent projects

Dr. Florian Krach
Friedrich-Alexander-University od Erlangen-Nuremberg - Clinic
Stem Cell Biology

Prof. Dr. Gene Yeo
University of California, San Diego
Sanford Consortium for Regenerative Medicine

Investigations on TDP-43-function in sporadic ALS and familial ALS with TDP-43 mutations

ALS is a neurodegenerative disorder affecting motor neurons (MNs). Neuropathologically, it is characterized by cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43. Although 90% of cases occur sporadically (sALS), 10% of ALS cases occur in a mendelian pattern of inheritance (familial ALS, fALS). Interestingly, in a subset of fALS cases mutations in TDP-43 can be found but it is unknown whether these mutations correspond functionally to the aggregations seen in sALS. Hence, we propose to investigate this in patient stem cell-derived MNs of fALS patients with TDP-43 mutations, sALS cases with an increased insolubility of TDP-43 and healthy controls. We will apply eCLIP-seq to identify changes in the RNA-binding pattern, RNA-seq to delineate sALS/fALS-specific transcriptome changes and APEX2-proximity labeling to elucidate the TDP-43 interactome in the different states.


Primary project: TDP-43 pathology and cellular phenotypes in genome-engineered and iPSC-derived neurons of patients with ALS


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