Michael Landreh

Michael Landreh

Principal Researcher | Docent
Visiting address: Solnavägen 9, Biomedicum, 17165 Solna
Postal address: C1 Mikrobiologi, tumör- och cellbiologi, C1 MTC Arsenian Henriksson Landreh, 171 77 Stockholm

About me

  • Our research group focuses on the use of mass spectrometry (MS), a technique
    that allows us to determine the exact weight of biomolecules, to study how
    proteins recognise and bind their partners.
    Group Leader at the Department of Microbiology, Tumor and Cell Biology
    * 2007: “Heart of Biomedical Science” Prize of the Leiden University
    Medical Student Association (M.F.L.S.)
    * 2008-2012: Karolinska Ph.D. student scholarship (KID grant), 1.1 mSEK
    * 2014-2016: ERC Marie Curie Early Career Development Fellowship in Life
    Sciences, 2.2 mSEK
    * 2014-2016: Junior Research Fellowship, St. Cross College, Oxford
    * 2017-2021: Ingvar Carlsson Award, 4 mSEK
    Funding: Vetenskapsrådet, Cancerfonden, Olle Enkvists Stiftelse, Karolinska
    Institutet
    * 2002 - 2005: BSc in Molecular Biotechnology at the Universität zu
    Lübeck, Germany
    * 2005 - 2007: MSc in Biomedical Sciences, Leiden University Medical Center,
    Leiden, The Netherlands, and Howard Hughes Medical Institute & Department
    of Biology, University of Pennsylvania, Philadelphia, PA, USA.
    * 2008 - 2012: Ph.D. with Prof. Hans Jörnvall, Department of Medical
    Biochemistry and Biophysics, Karolinska Institutet, Stockholm,
    Sweden. Thesis: “Molecular mechanisms of amyloid regulation” [1]
    *Academic Appointments*
    * 2013 - 2014: Postdoctoral fellow with Prof. Jan Johansson, Department of
    Neuroscience, and Prof. Hans Jörnvall, Department of Medical Biochemistry
    and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    * 2014 - 2016: Marie Curie Career Development Fellow with Prof. Dame Carol
    Robinson FRS, Department of Chemistry, University of Oxford, UK
    * Since 2017: Assistant Professor in Mass Spectrometry in the group of Prof.
    Sir David Lane FRS, Department of Microbiology, Tumor and Cell Biology,
    Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden
    [1] https://openarchive.ki.se/xmlui/handle/10616/41280

Research

  • For a full publication list, please visit my Google Scholar page [1].
    (a.k.a. Michael Fitzen)
    -------- Mass spectrometry of protein interactions from cancer to memory -----
    All biological processes can be described as biomolecules “talking” to
    each other, providing cargo, information, or transportation. These events
    usually take the from of a direct physical contact, i.e. a non-covalent
    interaction, in which one molecule, most often a protein, binds to one or
    more partners, inducing a change in the three-dimensional structure. In this
    manner, proteins can keep in touch with their environment to control their
    function. For example, upon sensing a change in pH, sider silk proteins lock
    each other into infinite chains to form very stable scaffolds, and membrane
    proteins can recognise individual lipid molecules in their environment to
    tune their activity accordingly. Aberrant, -faulty- interactions, on the
    other hand, interfere with these processes and are therefore often associated
    with diseases. Some proteins interact with themselves and form toxic
    structures such as amyloid fibrils that eventually lead to degeneration of
    the affected tissue, as seen in e.g Alzheimer's disease. Similarly,
    destabilization and aggregation of the tumour suppressor p53 and its targets
    leads loss of cell cycle control and impaired DNA damage repair, giving rise
    to cancer. Therefore, it is important to understand how exactly proteins
    “talk” to each other, and use this information to find ways to prevent
    interactions from going wrong.
    Our group focuses on the use of mass spectrometry (MS), a technique that
    allows us to determine the exact weight of biomolecules, to study how
    proteins recognise and bind their partners. MS is well-suited for the study
    of transient interactions, large complexes and even unstable proteins, all of
    which are refractory to other structural biology methods like NMR and X-ray
    crystallography. For this purpose, we combine several complementary
    approaches:
    - In “native” MS, we gently transfer proteins together with their binding
    partners from physiological solutions into the vacuum inside the mass
    spectrometer and measure the weight and stability of the resulting complex.
    This reveals what type of interaction holds the partners together, and how
    many (and which) molecules are involved.
    - Hydrogen/deuterium exchange MS measures the incorporation of a chemical
    label (Deuterium) into the protein. Deuterium is incorporated into flexible
    and exposed parts of the protein. By measuring the resulting increase in
    weight, we are able to determine the stability and folding state of a
    protein, and even locate binding sites for tother proteins.
    - MS-based proteomics allows us to identify individual proteins from complex
    mixtures based on their unique mass “fingerprints”. Using individual
    proteins as bait, we are able to fish out their specific interaction partners
    and map upstream and downstream targets.
    The combination of all three techniques provides direct insights into several
    aspects of an interaction, but also generates constraints that can be used to
    direct computational modelling
    [1] https://scholar.google.se/citations?user=_hm34wkAAAAJ&hl=sv

Teaching

  • * 2004 - 2005 Lab courses and seminars in general and organic chemistry,
    medical program, University of Lübeck, Germany
    * 2008 - 2014: Lab courses, seminars, lectures and examiner for General
    and Organic Chemistry (biomedical program), Physiological
    Chemistry (medical program) Laboratory safety (medical and biomedical
    programs), Department of MedicalBiochemistry and Biophysics, Karolinska
    Institutet
    * 2014 - 2016: Academic Advisor for DPhil students, St Cross College,
    University of Oxford
    * Since 2017: Lectures and Seminars, General and Organic Chemistry courses,
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet

Articles

All other publications

Employments

  • Principal Researcher, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2022
  • Degree Of Doctor Of Philosophy, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 2012

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