MD/PhD fellowship regarding the neurodegenerative disorder BPAN

ß-propeller protein associated neurodegeneration (BPAN) is a rare condition belonging to a
group of neurological disorders collectively known as neurodegeneration with brain iron
accumulation (NBIA). All NBIA disorders show iron accumulation in the basal ganglia,
which can be diagnosed using magnetic resonance imaging. There is currently no established
therapy available to slow down or reverse the progression of these conditions. BPAN is
characterized by an early developmental delay that remains static until further deterioration in
adulthood, leading to muscle stiffness and dementia. Exome sequencing identified
heterozygous sporadic mutations in the WDR45 gene as a causative factor of BPAN.
Although WDR45 appears to be involved in autophagy, the precise molecular role of this
protein in this pathway remains to be elucidated. Moreover, it is totally unknown whether
WDR45 is also part of other cellular processes.

The goal of this project is to understand the cellular defects caused by the disease-associated
mutations in WDR45 that leads to BPAN pathophysiology. WDR45 functions will be
investigated in standard laboratory cell lines and also in neurons derived from induced
pluripotent stem cells (iPSCs) obtained from BPAN patients, before to determine the impact
of the BPAN-associated mutations on these functions. This project will involve cutting-edge
biochemical, immunofluorescence and electron microscopy techniques, and it will be carried
out in a highly dynamic, international and interactive fundamental research laboratory.

Interested and willing to learn more about this research topic? Please contact Prof. Fulvio
Reggiori, Department of Biomedical Sciences of Cells & Systems, UMCG, [email protected]