Analysis of the molecular function of ALMS1

01/10/2022 to 30/09/2025

The autosomal-recessive disorder Alström syndrome is caused by mutations in one gene, ALMS1,
and appears in a high variability in symptoms and severity. The symptoms reflect a ciliopathy, which
can lead to e.g. heart failure, obesity and retinal degeneration. Cilia are microtubule-based cell
protrusions, which are involved in multiple cellular and signalling processes. ALMS1 protein is thought
to be involved in cilia maintenance, transport and signalling processes. However, due to the protein
size of 461 kDa which makes ALMS1 analysis difficult, the molecular function of ALMS1 remained
elusive. Here, we aim at understanding the role of ALMS1 in different cilia-related processes in healthy
and mutant cells. First, we want to gain more information about the ALMS1 protein complex by
analysis of endogenously tagged ALMS1 cells generated using the CRISPR/Cas9 technique. Second,
the expression pattern and subcellular localization of ALMS1 and its interacting partners will be
analysed. Third, the effect of loss of ALMS1 as well as of specific mutations will be investigated.
Based on all data gained in this study, we aim to better understand the molecular function of ALMS1 in
cilia-related processes which can be used as basis to investigate tissue-specific and disease-related
processes in the future.