Example of a current/available student projects (Bachelor/Master/PhD)
A) The functional role of SORLA dimerization
SORLA related receptors of the VPS10p family have all been show to dimerize as well as many of its ligands and co-receptors are also dimers. However, it has not yet been convincingly demonstrated if and what determines SORLA dimerization. We wish to investigate the factors that regulate SORLA homodimer formation, including glycosylation status and intramolecular interactions.
B) Exploring SORLA sorting in the early secretory pathway
We have identified a small receptor domain that is central for the selective transport of sSORLA leaving the endoplasmatic reticulum. We are interested to identify binding partners for this receptor fragment and characterize how this may influence sorting in the secretory pathway.
C) How to distinguish between pathogenic and benign SORL1 variants
A huge number of SORL1 variants are identified in patients with Alzheimers disease. However, there is currently no efficient method to predict if a variant is pathogenic or benign. We wish to establish functional assays to characterize variant pathogenicity for clinical practice.
Lab background:
The research in our laboratory has a focus on understanding the underlying molecular mechanisms of neurodegeneration as it occurs during dementia. Our most important findings include the description of the fourth autosomal dominant gene SORL1 as a sorting receptor for the Amyloid precursor protein and its involvement in Alzheimer’s disease.
Methods:
Biochemical and cell biological studies of neuronal cultures, including transfection of cells and analysis by Western blot and ELISA of amyloidogenic processing pathways. Cellular localization studies using in-situ hybridization methodologies and immunocytochemistry.
The successful applicant is:
Ambitious, hard working, and intelligent.
Other (master/PhD) projects available:
1) Alternative splice variants of SORL1 leads to local synaptic translation of a truncated receptor protein.
2) The physiological role of SORL1 during eye development and cataractogenesis.
