Heidi Kaastrup Müller - Molecular Neuropsychiatry

Our group focuses on the molecular basis of neuropsychiatric disorders and the processes underlying effective treatments by integrating animal models with molecular, biochemical, pharmacological and behavioral approaches.

Research focus

    • Molecular and functional mechanisms involved in the antidepressant effect of ketamine.
    • Exploration of the antidepressant potential of the psychedelic compound psilocybin.
    • The role of neuroglobin in sleep and neuroplasticity.
    • Compromised blood-brain barrier permeability in response to stress.
    • Identification and characterization of novel interacting partners of key proteins (Monoamine Transporters and Sortilin) involved in the development or treatment of psychiatric disorders.
    • Fluorescence-based functional studies of neurotransmitter transporters (Incorporating Unnatural Amino Acids).

      Aim

      The unifying aim of our current research activities is to provide information that advance our understanding of the neurobiological mechanisms involved in the pathophysiology of depression. The latent response to current available antidepressants and the prevalence of treatment-resistant depression emphasize the need for continuing research into alternative treatments. Our goal is to identify new potential targets for acute pharmacological treatment of depression and to provide translational perspectives for differentiation of patients for individualized and improved treatment.

      Main research methods

      • Studies of neurotransmitter release using superfused synaptosomes (Fig. 1)
      • 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 from R&D Systems)
      • Gel Doc EZ-Imager (Bio-Rad) for total protein normalization of Western blots
      • Bioluminescence resonance energy transfer (BRET)
      • Yeast two-hybrid screening (Split-ubiquitin system) (Fig. 2)
      • Cell culturing
      • siRNA analysis
      • Co-immunoprecipitation
      • GST-Pulldown
      • Cell-surface Biotinylation
      • Cloning, mutagenesis, DNA sequencing

      Available projects

      We offer Bachelor, Master, or Research Year projects within all aspects of our research focus. The projects are particularly relevant for students with a background in molecular biology, molecular medicine, or medicine. We support collaborative projects within our unit as well as multidisciplinary collaborations with external groups.

      Please contact Heidi Kaastrup Müller (heidi.muller@clin.au.dk) for further information.

      Figure 1: Superfusion
      Figure 2: YTH system
      Figure 1: Superfusion
      Figure 2: YTH system