Olav Andersen Lab

Figure legend: Schematic overview of the mammalian members of the low-density lipoprotein receptor and the sortilin receptor families showing their structural elements. Ongoing projects focus on the mosaic receptor molecule sorLA (LR11) and aim to understand and cure neurodegenerative disorders including Alzheimer’ disease. Examples of cellular receptor:receptor interaction studies, transgenic animal models, live-cell imaging, and structural characterization of receptor:ligand interactions are indicated by the surrounding research panels.

Group Leader

Olav Andersen
Associate professor, PhD
More information

RESEARCH
Our research moved into new laboratories in August 2010 at the Department of Medical biochemistry, now part of the new Institute for Biomedicine. Our key interest is to provide functional characterization of sorLA and its homologue receptors of the VPS10p and LDL receptor families in the central nervous system. These receptors have been found to partake in a plethora of neuronal functions, and receptor dysfunction is therefore critically associated with neurological diseases.

In particular, we have identified a role of sorLA as sorting receptor for the Amyloid precursor protein (APP), and uncovered sorLA as risk factor for Alzheimer’s disease. Our current studies focus to elucidate the pathogenic mechanisms that link sorLA to neurodegenerative disorders, and trying to model the disease in cells and animals with the aim to identify novel therapeutic strategies. This is done using a wide range of biochemical, molecular, cellular and genetic tools in close collaboration with expert national and international collaborators.

RESEARCH INTERESTS
Identify novel ligands for the receptor families, and to understand the molecular determinants of receptor:ligand complexes (i.e. solving the structure of the sorLA:APP complex)

Elucidate protein networks centered around the VPS10p receptors (characterize multi-protein complexes from neurons)

Neuronal sorting mechanisms (i.e. live-cell imaging)

Understanding the physiological function of receptor:ligand complexes (i.e. investigate the role of sorLA:APP complex formation in the retina)

Study receptor activity regulation (i.e. promoter activity, transcription factors, SNP analysis, splice variants, post-translational modifications)

Developing new assays to study receptor functions

METHODOLOGIES
We have experience with biochemical techniques, cell biological assays, and phenotypic characterization of transgenic animal models. However, we are also continuously trying to develop new technologies to improve our methodological repertoire, and welcome all such novel proposals.

Biochemical studies (recombinant protein expression and purification; co-immunoprecipitation; Western blotting; Alpha technology; ELISA; protein interaction studies by surface plasmon resonance and isothermal titration calorimetry)

Molecular and Cellular biology (RT-PCR; cloning of eukaryotic expression vectors and generation of stable cell lines; cell culturing; pulse-chase receptor maturation; immunostaining; confocal microscopy; live-cell microscopy; fluorescence lifetime imaging microscopy; proximity ligation assay/duolinkI

Transgenic animal models (preparation of primary cultures, immunostainings, phenotype characterization)

COLLABORATORS & Centers

  • Anders Nykjær, Jens Nyengaard, Kimmo Jensen and colleagues at the MIND center, Aarhus University, Denmark
  • Thomas E. Willnow, Max-Delbrück-Center for molecular medicine, Berlin, Germany
  • Roberto Cappai, Melbourne University, Australia
  • Matthew Seaman, Cambridge University, UK
  • Birthe B. Kragelund, Copenhagen University, Denmark
  • Mark E. West, Aarhus University, Denmark
  • Juan Troncoso, Johns Hopkins, Baltimore, USA
  • Göran Larson, Göteborg University, Sweden
  • Gerd Multhaup, Free University, Berlin, Germany
  • Peter St. Georg-Hyslop, Cambridge University, UK

(And many more - please refer to the list of publications for a more complete list of collaborations)

RESEARCH GROUP MEMBERS
Arnela Mehmedbasic, PhD student; Annemarie Poulsen, Research Assistant; Betina Bjerregaard Nielsen, MSc student; Sofie Kjellerup Christensen, MSc-student; Anne Kathrine Ivarsen, BSc-student; Sandra Bonnesen, technician; Ann Rosborg Kristensen, technichan

The group supervises a number of bachelor students and welcome exchange students and research year students                                                         

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Revideret 03.08.2016