Michael Landreh

Michael Landreh

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

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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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