Dr. Daniel Mann

Postdoctoral Scientist

As a trained structural biologist I am interested in how enzymes function at the molecular level. My current topic of research is how heterotrimeric G-Proteins function at (sub-)atomic resolution. These proteins function like molecular switches, that are activated by binding of a GTP molecule at the Gα subunit and inactivated via GTP hydrolysis. This switch mechanism maintains essential physiological processes such as vision, scent or blood pressure regulation. When mutated or modified these proteins are responsible for severe diseases like cholera, pertussis and cancer. A detailed understanding of these mechanisms is the prerequisite of a development of personalized treatments against these diseases.

Home Department: Department of Biophysics, Ruhr University Bochum

Office Address: ND 04 / 67

Office Phone: (+49) 234 32 28363

Email Address: daniel.mann@bph.rub.de

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Foto-Mann

Research Interests

I strongly believe that only the combination of experiment and theory can result in reliable models of how proteins work. Therefore I work interdisciplinary in both areas and try to combine both approaches, mainly via the precise measurement of FTIR signals and their re-calculation from quantum mechanical (QM) calculations, that enable interpretation of the experiments with subatomic resolution. Currently I apply the following methods:

  • Heterologous protein cloning, expression, purification, modification
  • Biochemical characterization (e.g. measurement of multiple turnover kinetics via HPLC)
  • Fluorescence Spectroscopy (Trp-Fluorescence, FRET)
  • Fourier transform infrared (FTIR) Spectroscopy
  • Theoretical infrared Spectroscopy from QM/MM calculations
  • MD Simulations
  • QM/MM Simulations

I am interested in GTPases and ATPases, mainly:

  • Gα subunit of heterotrimeric G-Proteins (Gαi, Gαs)
  • Cholera Toxin impact on Gαs
  • Ras GTPase
  • MSBA ATPase
  • Arf GTPase
  • Arl GTPase
Cover

Time resolved FTIR difference spectroscopy yields simultaneously infrared signals of the educt, the product and the protein groups that are ultra sensitive to changes in their direct environment (phosphates: 1 cm-1 corresponds to a change in a P-O bond length of 0.001 nm). Kinetic investigations elucidate the effect of point mutations (e.g. mutation of the intrinsic arginine finger (red)) or effector binding (e.g. binding of the GAP RGS4 (green))

FTIR spectroscopy

Education

  • 2017 Postdoctoral Scientist Ruhr University Bochum, Department of Biophysics
  • 2013-2017 PhD Student (Graduate School of Biosciences IGB), Ruhr University Bochum, Department of Biophysics, Advisor: PD Dr. Carsten Kötting, Summa cum laude
  • 2012 Master of Science (Structural Biology), Ruhr University Bochum, Department of Biophysics "Experimental and theoretical investigations on the Gα(s) subunit of heterotrimeric G-Proteins" Advisor: PD Dr. Carsten Kötting
  • 2010 Bachelor of Science (Biology), Ruhr University Bochum, Department of Biophysics "MD simulations of Ras dimerization and membrane binding" Advisor: PD Dr. Jürgen Schlitter

Publications

Peer reviewed articles

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  • Gerwert K., Mann D., Kötting C. Common mechanisms of catalysis in small and heterotrimeric GTPases and their respective GAPs Biol.Chem. (2017) ISSN (Online) 1437-4315, ISSN (Print) 1431-6730 DOI: https://doi.org/10.1515/hsz-2016-0314
  • Mann D., Höweler U., Kötting C., Gerwert K. Elucidation of Single Hydrogen Bonds in GTPases via Experimental and Theoretical Infrared Spectroscopy Biophys.J. (2017) 1(112), 66-77
  • Mann D., Teuber C., Tennigkeit S.A., Schröter G., Gerwert K, Kötting C. Mechanism of the intrinsic arginine finger in heterotrimeric G-proteins PNAS (2016) 50(113), E8041-8050
  • Schröter G.*, Mann D.*, Kötting C., Gerwert K. Integration of Fourier Transform Infrared Spectroscopy, Fluorescence Spectroscopy, Steady-State Kinetics and Molecular Dynamics Simulations of Gαi1 distinguishes between the GTP Hydrolysis and GDP Release Mechanism J.Biol.Chem. (2015) 290(28) 17085-17095 (* shared first author)
  • Güldenhaupt J., Rudack T., Bachler P., Mann D., Triola G., Waldmann H., Kötting C., Gerwert K. N-Ras Forms Dimers at POPC Membranes Biophys.J. (2012) 103, 1585-1593

Other publications

  • Mann D., Kötting C., Gerwert K. Der Computer als Mikroskop - Wie biomolekulare Simulationen helfen, Proteinmechanismen mit hoher zeitlicher und räumlicher Auflösung zu dekodieren GIT Labor (Wiley) 3/2017
  • Mann D. et al. FTIR Spectroscopy enables research at the subatomic level BioPhotonics (Photonics Media) February/March 2017

Conference Participations

  • Talk "Mechanism of the Intrinsic Arginine Finger in Heterotrimeric G-Proteins" European Conference on the Spectroscopy of Biomolecules (ECSBM) 2017, Amsterdam, NL, 11.-14.9.2017
  • Poster "Mechanism of the Intrinsic Arginine Finger in Heterotrimeric G-Proteins Investigated via Experimental and Theoretical FTIR Spectroscopy" General Assembly of the German Bunsen Society 2017: Physical Chemistry for Life Sciences, Kaiserslautern, 25.-28.5.2017
  • Talk "Mechanisms of GTP Hydrolysis in Heterotrimeric GTPases Elucidated via Theoretical IR Spectroscopy" Computer Simulation and Theory of Macromolecules, Hünfeld, 24.-25.3.2017
  • Poster „Gai1 considered from all sides – monitoring single turnover-, multiple turnover- and nucleotide exchange kinetics of a central molecular switch“ 16th European Conference on the Spectroscopy of Biological Molecules, Bochum, 6.9.- 10.9.2015
  • Talk „Gai1 considered from all sides – monitoring single turnover-, multiple turnover- and nucleotide exchange kinetics of a central molecular switch “ 4th SFB642 Summer School, Velen 11.5.-13.5.2015
  • Poster „Gai1 considered from all sides – monitoring single turnover-, multiple turnover- and nucleotide exchange kinetics of a central molecular switch“ Joint Meeting of the Dutch and German Biophysical Society: Structure, Dynamics and Interactions of Biomolecules, Hünfeld, 26.2.-28.2.2015
  • Talk „Biophysical investigations on the stimulatory and inhibitory isoforms of the Ga subunit of heterotrimeric G proteins“ GTPases: Mechanisms, Interactions and Applications, Cold Spring Harbor Asia Conference, Suzhou, China, 22.9.-26.9.2014
  • Poster „G(i) Alpha – Biophysical Investigations of a Central Molecular Switch“ Computer Simulation and Theory of Macromolecules, Hünfeld, 11.4.-12.4.2014
  • Poster „Biophysical Investigations on the Stimulatory and Inhibitory Isoforms of the Ga Subunit of Heterotrimeric G Proteins“ 3rd SFB642 Summer School, Münster 30.9.- 2.10.2013
  • Poster „Biophysical Investigations on the G(s) Alpha Subunit of Heterotrimeric G- Proteins“ Computer Simulation and Theory of Macromolecules, Hünfeld, 26.4.- 27.4.2013
  • Poster „Biophysical Investigations on the GaS Subunit of Heterotrimeric G-Proteins“ Joint Meeting of the British and German Biophysical Society: Function, Structure and Dynamics of Biomolecules, Hünfeld, 21.3.-23.3.2013
  • Poster „Biophysical Investigations on the Gas Subunit of Heterotrimeric G Proteins“ Small GTPases at different scales: Proteins, Membranes, Cells, Bochum, 24.9.- 28.9.2012
  • Poster „Biophysical Investigations on the G Alpha S Subunit of Heterotrimeric G- Proteins“ Computer Simulation and Theory of Macromolecules, Hünfeld, 20.4.- 21.4.2012

Press Releases

Journal Covers

Biophys.J. 103 (2012) c1
J.Biol.Chem. 290(28) (2015) c1
Biophys.J. 112 (2017) c1
Biol.Chem. 398 (2017) c1