Heidi Kaastrup Müller - Molecular Neuropsychiatry
Our current research focuses on understanding the molecular mechanisms controlling proteolytic processing of amyloid precursor protein, p75NTR and sortilin in neurodegenerative and neuropsychiatric disorders and evaluating potential approaches to target these processes for therapeutic purposes. We are particularly interested in regulatory mechanisms of ectodomain shedding mediated by protein-protein interactions and processes modulated by membrane cholesterol levels.
A second topic of research interest is molecular mechanisms contributing to fast-acting antidepressant effects of ketamine and psychedelics. Studies include receptor signaling, trafficking, and protein-protein interactions.
Research focus
Current research activities:
- Regulation of sortilin ectodomain shedding by the neuron-specific proteins NSG1 and NSG2
- Functional investigation of sortilin SNVs in frontotemporal lobe dementia
- Regulation of APP proteolytic cleavage by interacting proteins
- Regulation of p75NTR proteolytic cleavage by interacting proteins
- Collaborating projects: Molecular mechanisms underlying the actions of rapid acting antidepressants (ketamine, CBD, psilocybin)
- Collaborating projects: Molecular and functional studies of the Serotonin Transporter
Aim
We aim to discover molecular targets and mechanisms that can be translated into novel therapeutic strategies for neuropsychiatric and neurodegenerative disorders.
Main research methods
- Yeast two-hybrid screening
- Isolation and culture of rat/mouse embryonic neuronal cells
- Cell culturing (HEK293MSR, HEK293T, RN46A, SH-SY5Y)
- Transfection (Ecotransfect, Lipofectamine, Electroporation via Nucleofector)
- Subcellular fractionation by ultracentrifugation; synaptosomes, synaptic vesicles, postsynaptic membranes
- Western blot (two-color detection with infrared fluorescence - compatible with proteome profiler Arrays)
- Ectodomain shedding assay
- Exosomes
- Bioluminescence resonance energy transfer (BRET)
- siRNA-mediated gene silencing
- Co-immunoprecipitation
- GST-Pulldown
- Cell-surface Biotinylation
- On cell ELISA/Western blot
- Cloning, mutagenesis, DNA sequencing
Available projects
We have projects available for Master, PhD, and Research Year students. The projects are particularly relevant for students with a background in molecular biology, molecular medicine, medicinal chemistry or medicine. We support collaborative projects within our unit as well as collaborations with external groups.
Please contact Heidi Kaastrup Müller (heidi.muller@clin.au.dk) for further information.
