̽����ѡ

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, Docent (2022)
* 2007: “Heart of Bio̽����ѡ 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, SSMF, KAW, Cancerfonden, Olle Enkvists Stiftelse, Karolinska 
Institutet
* 2002 - 2005: BSc in Molecular Biotechnology at the Universität zu
Lübeck, Germany
* 2005 - 2007: MSc in Bio̽����ѡ 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, ̽����ѡ, 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, ̽����ѡ, Stockholm, Sweden.
* 2014 - 2016: Marie Curie Career Development Fellow with Prof. Dame Carol
Robinson FRS, Department of Chemistry, University of Oxford, UK
* 2017-2021: 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, ̽����ѡ, Stockholm, Sweden

* Since 2022: Associate professor and group leader, Department of Microbiology, Tumor and Cell Biology,
Science for Life Laboratory, ̽����ѡ, Stockholm, Sweden, and Senior Lecturer in Molecular BIophysics, Institute of Cell and Molecuar Biology, Uppsala University, Sweden

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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.

A particularly challenging type of portein interactions drives the assembly of membraneless organlles. Here, disordered, flexible proteins interact with each other through non-specific contacts, forming a liquid-like, separate phase that in turn recruits additional proteins to assemble a functional superstructure, Aberrations in this process, called liquid-liquid phase separation (LLPS), are a stepping-stone for protein aggregation and cancer.

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.

We employ these methods to study how proteins assemble via LLPS, and how we can target the "fuzzy" interactions between disordered proteins to prevent disease.

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