This $1,029,657 five-year Project Grant award from the National Institute on Aging (under CFDA 93.866 Aging Research) supports research to investigate the role of TDP-43 protein mislocalization, structure, and post-translational modifications in the neuropathological heterogeneity of TDP-43 proteinopathies. The primary awardee, Trustees of Indiana University (doing business as Indiana University Indianapolis), will leverage expertise in neuropathology, molecular genetics, protein characterization, and advanced imaging techniques to:
- Map TDP-43 inclusions, misfolded TDP-43, and glial response in different neuronal and glial populations to determine how TDP-43 amyloid folding relates to neuropathological phenotypes.
- Identify novel post-translational modifications associated with misfolded TDP-43 and assess differences in TDP-43 seeding properties.
- Use cryo-electron microscopy to determine the structures of TDP-43 amyloid filaments.
A sub-award to UK Research & Innovation will provide intellectual expertise and services related to the extraction and analysis of TDP-43 filaments from brain tissue samples.
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