Heidi Kaastrup Müller - Molecular Neuropsychiatry

Our research focuses on the molecular correlates of treatment response to rapid acting antidepressants with particular emphasis on ketamine and psilocybin. We are also interested in the regulatory mechanisms controlling the trafficking and function of the sortilin receptor in health and disease states.

Research focus

Current research activities are targeted into three major focus areas:

  • Molecular mechanisms underlying the rapid antidepressant action of ketamine. The discovery that ketamine, an agent that has been used for more than 50 years to induce anesthesia, can produce rapid, robust and relatively sustained antidepressants effects in treatment-resistant patients, represents the most important breakthrough in antidepressant treatment for decades. In the search for molecular correlates to the behavioral action of ketamine, we use rodent models to study both pre- and postsynaptic changes in protein-protein interactions, protein expression levels, subcellular localization, and phosphorylation status.

  • Molecular responses to psilocybin. Psilocybin, a naturally occurring psychedelic compound found in magic mushrooms, is gaining increasing attention for its potential therapeutic capacity in the treatment of depression, and was recently granted a Breakthrough Therapy designation by the FDA for the second time in a year. To provide novel insights into psilocybin’s mechanism of action we are investigating its downstream molecular effects including gene and protein expression profiling of inflammatory and neuroplasticity markers.

  • Regulation of the sortilin receptor by novel interacting protein partners. The sortilin receptor is an intriguing protein serving multiple functions as a sorting molecule and cell surface receptor of a variety of ligands. Dysfunction of the sortilin receptor has been linked to neuropsychiatric and degenerative diseases including depression, Alzheimer’s disease, and frontotemporal lobar dementia. Therefore, proteins that via binding to sortilin can influence disease mechanisms are particular interesting and could serve as important novel targets for the development of disease modifying drugs. We have identified a panel of novel sortilin interacting proteins, which are currently under investigation for their effects on sortilin trafficking, localization and function under various conditions.


We aim to discover molecular targets and mechanisms that can be translated into novel therapeutic strategies for neuropsychiatric and neurodegenerative disorders.

Main research methods

  • Identification of novel protein interactions (yeast two-hybrid screening and immunoprecipitation coupled to mass spectrometry)
  • Isolation and culture of rat/mouse embryonic neuronal cells
  • Cell culturing (HEK293MSR, HEK293T, RN46A, and SH-SY5Y cells)
  • Transfection (Ecotransfect, Lipofectamine, Electroporation via Nucleofector)
  • Subcellular fractionation by ultracentrifugation; synaptosomes, synaptic vesicles, postsynaptic membranes
  • Immunohistochemistry
  • Morphological analysis (Golgi-Cox)
  • Animal models of depression
  • Pharmacological treatments/manipulations
  • Two-color Western blot detection with infrared fluorescence (Licor)(compatible with proteome profiler Arrays)
  • 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.