F.N. Brinkman MSc (Fleur)
PhD candidate - Biomolecular Chemistry
Inclusion body myositis (IBM) is a progressive muscle disease of which the cause is not yet known. It has been found that at least one third of patients with IBM have autoantibodies directed against cytosolic 5’-nucleotidase 1A (cN1A). Recently, we found that cN1A can form distinct condensates in cultured cells, leading to a variety of questions that we hope to answer in this research project.
In this project we focus on two aspects: the anti-cN1A response in IBM patients and the intracellular accumulation of cN1A. By characterizing the anti-cN1A autoantibodies produced by IBM patients we want to elucidate the role of these antibodies in the pathogenesis of this disease. In addition, we want to study patient material to investigate whether the cN1A protein or its levels might be altered in patients. Furthermore, we will characterize cN1A accumulations at the molecular level. Proteins that co-localize within the cN1A-containing filamentous condensates will be identified using APEX proximity labeling. We are also interested to see which specific conditions drive filament assembly and disassembly. We will also characterize the dynamic nature of these filaments by looking at their mobility and structure. In collaboration with neurologists, the implications of the results obtained in vitro for the degeneration of IBM patient muscles will be investigated.