Fritz G Parak

Technische Universität München, München, Bavaria, Germany

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Publications (83)326.75 Total impact

  • Fritz Parak
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    ABSTRACT: A physicist who revitalized German science by creating a new type of spectroscopy.
    Nature 10/2011; 478(7369):325. DOI:10.1038/478325a
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    ABSTRACT: Freeze-dried perdeuterated sperm whale myoglobin was kept in a water-saturated atmosphere in order to obtain a hydration degree of 335 H(2)O molecules per one myoglobin molecule. Incoherent neutron scattering was performed at the neutron spectrometer TOFTOF at the FRM II in an angular range of q from 0.6 to 1.8 Å(-1) and a temperature range from 4 to 297 K. We used neutrons with a wavelength of λ αE 6 Å and an energy resolution of about 65 μeV corresponding to motions faster than 10 ps. At temperatures above 225 K, broad lines appear in the spectra caused by quasielastic scattering. For an explanation of these lines, we assumed that there are only two types of protons, those that are part of the hydration water (72%) and those that belong to the protein (28%). The protons of the hydration water were analyzed with the diffusion model of Singwi and Sjölander [Phys. Rev. 119, 863 (1960)]. In this model, a water molecule stays for a time τ(0) in a bound state performing oscillatory motions. Thereafter, the molecule performs free diffusion for the time τ(1) in a nonbound state followed again by the oscillatory motions for τ(0) and so forth. We used the general formulation with no simplifications as τ(0)≫τ(1) or τ(1)≫τ(0). At room temperature, we obtained τ(0) αE 104 ps and τ(1) αE 37 ps. For the protein bound hydrogen, the dynamics is described by a Brownian oscillator where the protons perform overdamped motions in limited space.
    Physical Review E 10/2011; 84(4 Pt 1):041930. DOI:10.1103/PhysRevE.84.041930
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    ABSTRACT: Structural studies of biological macromolecules are severely limited by radiation damage. Traditional crystallography curbs the effects of damage by spreading damage over many copies of the molecule of interest in the crystal. X-ray lasers offer an additional opportunity for limiting damage by out-running damage processes with ultrashort and very intense X-ray pulses Such pulses may allow the imaging of single molecules, clusters; Or nanoparticles: Coherent flash Imaging Will also open up new avenues for structural studies on nano- and microcrystalline substances. This paper addresses the theoretical potentials and limitations of nanocrystallography with extremely intense coherent X-ray pulses. We use urea nanocrystals as a model for generic biological substances and simulate the primary and secondary ionization dynamics in the crystalline sample. The results establish conditions for ultrafast single shot nanocrystallography diffraction experiments as a function of X-ray fluence, pulse duration, and the size of nanocrystals. Nanocrystallography using ultrafast X-ray pulses has the potential to open up a new route in protein crystallography to solve atomic structures of many systems that remain Inaccessible using conventional X-ray sources.
    ACS Nano 01/2011; 5(1):139-146. DOI:10.1021/nn1020693
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    ABSTRACT: Structural studies of biological macromolecules are severely limited by radiation damage. Traditional crystallography curbs the effects of damage by spreading damage over many copies of the molecule of interest. X-ray lasers, such as the recently built LINAC Coherent Light Source (LCLS), offer an additional opportunity for limiting damage by out-running damage processes with ultrashort and very intense X-ray pulses. Such pulses may allow the imaging of single molecules, clusters or nanoparticles, but coherent flash imaging will also open up new avenues for structural studies on nano- and micro-crystalline substances. This paper addresses the theoretical potentials and limitations of nanocrystallography with extremely intense coherent X-ray pulses. We use urea nanocrystals as a model for generic biological substances and simulate primary and secondary ionization dynamics in the crystalline sample. Our results establish conditions for ultrafast nanocrystallography diffraction experiments as a function of fluence and pulse duration. Comment: 6 pages, 4 color figures
  • EPL (Europhysics Letters) 10/2009; 88(2). DOI:10.1209/0295-5075/88/29901
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    ABSTRACT: Rhodnius prolixus Nitrophorin 4 (abbreviated NP4) is an almost pure beta-sheet heme protein. Its dynamics is investigated by X-ray structure determination at eight different temperatures from 122 to 304 K and by means of Mössbauer spectroscopy. A comparison of this beta-sheet protein with the pure alpha-helical protein myoglobin (abbreviated Mbmet) is performed. The mean square displacement derived from the Mössbauer spectra increases linearly with temperature below a characteristic temperature T(c). It is about 10 K larger than that of myoglobin. Above T(c) the mean square displacements increase dramatically. The Mössbauer spectra are analyzed by a two state model. The increased mean square displacements are caused by very slow motions occurring on a time scale faster than 140 ns. With respect to these motions NP4 shows the same protein specific modes as Mbmet. There is, however, a difference in the fast vibration regime. The B values found in the X-ray structures vary linearly over the entire temperature range. The mean square displacements in NP4 increase with slopes which are 60% larger than those observed for Mbmet. This indicates that nitrophorin has a larger structural distribution which makes it more flexible than myoglobin.
    Biophysics of Structure and Mechanism 04/2009; 38(5):687-700. DOI:10.1007/s00249-009-0427-z
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    ABSTRACT: A physical model is reviewed which explains different aspects of protein dynamics consistently. At low temperatures, the molecules are frozen in conformational substates. Their average energy is 3/2RT. Solid-state vibrations occur on a time scale of femtoseconds to nanoseconds. Above a characteristic temperature, often called the dynamical transition temperature, slow modes of motions can be observed occurring on a time scale between about 140 and 1 ns. These motions are overdamped, quasidiffusive, and involve collective motions of segments of the size of an alpha-helix. Molecules performing these types of motion are in the "flexible state". This state is reached by thermal activation. It is shown that these motions are essential for conformational relaxation. Based on this picture, a new approach is proposed to understand conformational changes. It connects structural fluctuations and conformational transitions.
    Journal of Biological Physics 12/2008; 33(5-6):371-87. DOI:10.1007/s10867-008-9102-3
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    ABSTRACT: The magnetic properties and results from X-ray structure analysis for a new pair of iron(II) spin-crossover complexes [FeL1(meim) 2](meim) ( 1(meim)) and [Fe 2L2(meim) 4](meim) 4 ( 2(meim) 4), with L1 being a tetradentate N 2O 2 (2-) coordinating Schiff-base-like ligand [([3,3']-[1,2-phenylenebis(iminomethylidyne)]bis(2,4-pentane-dionato)(2-)N,N',O (2),O (2)'], L2 being an octadentate, dinucleating N 2O 2 (2-) coordinating Schiff-base-like ligand [3,3',3'',3''']-[1,2,4,5-phenylenetetra(iminomethylidyne)]tetra(2,4-pentanedionato)(2-) N, N', N'', N''', O (2), O (2) ', O (2) '', O (2) '''], and meim being N-methylimidazole, are discussed in this work. Crystalline samples of both complexes show a cooperative spin transition with an approximately 2-K-wide thermal hysteresis loop in the case of 1(meim) ( T 1/2 increase = 179 K and T 1/2 decrease = 177 K) and an approximately 21-K-wide thermal hysteresis loop in the case of dinuclear complex 2(meim) 4 ( T 1/2 increase= 199 K and T 1/2 decrease= 178 K). For a separately prepared powder sample of 2, a gradual spin transition with T 1/2 = 229 K is observed that was additionally followed by Mossbauer spectroscopy. The results from X-ray structure analysis give a deeper insight into the molecule packing in the crystal and, by this, help to explain the increase of cooperative interactions during the spin transition when going from the mononuclear to the dinuclear complex. Both compounds crystallize in the triclinic space group P1, and the X-ray structure was analyzed before and after the spin transition. The change of the spin state at the iron center is accompanied by a change of the O-Fe-O angle, the so-called bite of the equatorial ligand, from about 109 degrees in the high-spin state to 89 degrees in the low-spin state. The cooperative interactions responsible for the thermal hysteresis loop are due to elastic interactions between the complex molecules in both cases. However, due to the higher symmetry of the dinucleating ligand in 2(meim) 4, a 3D network of short contacts is formed, while for mononuclear complex 1(meim), a 2D layer of linked molecules is observed. The spin transition was additionally followed in solution using (1)H NMR spectroscopy for both complexes. In both cases, a gradual spin transition is observed, and the increase of cooperative interactions when going from the mononuclear to the dinuclear system is solely attributed to the extended network of intermolecular contacts.
    Inorganic Chemistry 11/2008; 47(22):10779-87. DOI:10.1021/ic801388a
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    ABSTRACT: Two new spin-crossover complexes, [FeL1(phpy)2] (1) and [FeL2(phpy)2](phpy) (2), with L1 and L2 being tetradentate N2O22–-coordinating Schiff-base-like ligands {L1 = (E,E)-[diethyl 2,2′-[1,2-phenylenebis(iminomethylidyne)]bis(3-oxobutanoato)(2–)-N,N′,O3,O3′], L2 = [(3,3′)-[1,2-phenylenebis(iminomethylidyne)]bis(2,4-pentanedionato)(2–)-N,N′,O2,O2′]and phpy = 4-phenylpyridine} have been investigated using temperature-dependent susceptibility and photomagnetic measurements, as well as Mössbauer spectroscopy and X-ray structure analysis. Compound 1 shows a cooperative spin transition with a thermal hysteresis loop approximately 4 K wide (T1/2 = 232 K and T1/2 = 236 K). The spin transition of 2 is gradual with T1/2 ≈ 290 K. Results from X-ray structure analysis indicate that the cooperative interactions are due to elastic interactions with several intense C–C contacts in the case of 1. The change of the spin state at the iron centre is accompanied by a change of the O–Fe–O angle, the so-called bite of the equatorial ligand, from 107° in the high-spin state to 89° in the low-spin state. Reflectivity measurements of 1 indicate that the Light-Induced Excited Spin State Trapping (LIESST) effect occurs at the sample surface at low temperatures. In the bulk solid, photomagnetic properties with a photoexcitation level of 30 % and a T(LIESST) value of 41 K are observed using a SQUID magnetometer. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
    Berichte der deutschen chemischen Gesellschaft 11/2008; 2008(31):4891 - 4898. DOI:10.1002/ejic.200800420
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    ABSTRACT: Radiation damage is an unavoidable process when performing structural investigations of biological macromolecules with X-rays. In crystallography this process can be limited through damage distribution in a crystal, while for single molecular imaging it can be outrun by employing short intense pulses. Secondary electron generation is crucial during damage formation and we present a study of urea, as model for biomaterial. From first principles we calculate the band structure and energy loss function, and subsequently the inelastic electron cross-section in urea. Using Molecular Dynamics simulations, we quantify the damage and study the magnitude and spatial extent of the electron cloud coming from an incident electron, as well as the dependence with initial energy. Copyright (C) EPLA, 2009
    EPL (Europhysics Letters) 08/2008; 85(1). DOI:10.1209/0295-5075/85/18005
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    ABSTRACT: In this work the hemoglobin conformational changes induced by changing the iron charge have been studied and compared with Myoglobin. Mössbauer spectroscopy was used to follow the change of the iron conformation. In order to compare the conformational relaxation of hemoglobin and myoglobin, and to study a possible influence of the quaternary structure, an intermediate metastable state of hemoglobin has been created by low temperature X-ray irradiation of methemoglobin. The irradiation reduces the Fe(III) of the heme groups to Fe(II) Low Spin, where the water is still bound on the sixth coordination. Heating cycles performed at temperatures from 140K to 200K allow the molecules to overcome an activation energy barrier and to relax into a stable conformation such as deoxy-hemoglobin or carboxy-hemoglobin, if CO is present. Slightly different structures (conformational substates) reveal themselves as a distribution of energy barriers (ΔG#). The distribution of the activation energy, for the decay of the Fe(II) Low Spin intermediate, has been fitted with a Gaussian. For comparison, published myoglobin data were re-analysed in the same way. The average energy value at characteristic temperature is very similar in case of myoglobin and hemoglobin. The larger Gaussian energy distribution for myoglobin with respect to hemoglobin shows that more conformational substates are available. This may be caused by a larger area exposed to water. In hemoglobin, part of the surface of the chains is not water accessible due to the quaternary structure.
    Hyperfine Interactions 07/2008; 185(1):103-110. DOI:10.1007/s10751-008-9813-7
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    ABSTRACT: Two new spin crossover complexes [FeL(py)(2)] (1) and [FeL(DMAP)(2)] (2) with L being a tetradentate N(2)O(2)(2-) coordinating Schiff-base-like ligand [([3,3']-[1,2-phenylenebis(iminomethylidyne)]bis(2,4-pentanedionato)(2-)-N,N',O(2),O(2)'], py = pyridine and DMAP = p-dimethylaminopyridine have been investigated using temperature-dependent susceptibility and thermogravimetric and photomagnetic measurements as well as Mössbauer spectroscopy and X-ray structure analysis. Both complexes show a cooperative spin transition with an approximately 9 K wide thermal hysteresis loop in the case of 2 (T(1/2) upward arrow = 183 K and T(1/2) downward arrow = 174 K) and an approximately 2 K wide thermal hysteresis loop in the case of the pyridine diadduct 1 (T(1/2) upward arrow = 191 K and T(1/2) downward arrow = 189 K). The spin transition was additionally followed by different temperature-scanning calorimetry and Mössbauer spectroscopy for 2, and a good agreement for the transition temperatures obtained with the different methods was found. Results from X-ray structure analysis indicate that the cooperative interactions are due to elastic interactions in both compounds. They are more pronounced in the case of 2 with very short intermolecular iron-iron distances of 7.2 A and several intense C-C contacts. The change of the spin state at the iron center is accompanied by a change of the O-Fe-O angle, the so-called bit of the equatorial ligand, from 108 degrees in the high-spin state to 90 degrees in the low-spin state. The reflectivity measurements of both compounds give at low temperature indication that at the sample surface the light-induced excited spin state trapping (LIESST) effect occurs. In bulk condition using a SQUID magnetometer the complex 2 displays some photomagnetic properties with an photoexcitation level of 60% and a T(LIESST) value of 53 K.
    Inorganic Chemistry 02/2008; 47(2):487-96. DOI:10.1021/ic070067o
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    ABSTRACT: The difference between success or failure of chemotherapy depends not only on the drug itself but also on how it is delivered to its target. Biocompatible ferrofluids (FF) are paramagnetic nanoparticles, that may be used as a delivery system for anticancer agents in locoregional tumor therapy, called “magnetic drug targeting”. Bound to medical drugs, such magnetic nanoparticles can be enriched in a desired body compartment (tumor) using an external magnetic field, which is focused on the area of the tumor. Through this form of target directed drug application, one attempts to concentrate a pharmacological agent at its site of action in order to minimize unwanted side effects in the organism and to increase its locoregional effectiveness. Tumor bearing rabbits (VX2 squamous cell carcinoma) in the area of the hind limb, were treated by a single intra-arterial injection (A. femoralis) of mitoxantrone bound ferrofluids (FF-MTX), while focusing an external magnetic field (1.7 Tesla) onto the tumor for 60 minutes. Complete tumor remissions could be achieved in these animals in a dose related manner (20% and 50% of the systemic dose of mitoxantrone), without any negative side effects, like e.g. leucocytopenia, alopecia or gastrointestinal disorders. The strong and specific therapeutic efficacy in tumor treatment with mitoxantrone bound ferrofluids may indicate that this system could be used as a delivery system for anticancer agents, like radionuclids, cancer-specific antibodies, anti-angiogenetic factors, genes etc.
    01/2008: pages 233-251;
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    ABSTRACT: The cellular prion protein (PrP(C)) is a copper binding protein. The molecular features of the Cu(2+) binding sites have been investigated and characterized by spectroscopic experiments on PrP(C)-derived peptides and the correctly folded human full-length PrP(C) (hPrP-[23-231]). These experiments allowed us to distinguish two different configurations of copper binding. The different copper complexes depend on sequence context, buffer conditions and stoichiometry of copper. The combined information of spectroscopic data from our EXAFS, EPR and ENDOR experiments was used to create models for these two copper complexes. A large number of conformations of these models were calculated using molecular mechanics computations, and the simulated spectra of these structures were compared with our experimental data. Common features and differences of the copper binding motifs are discussed in this paper and it remains for future investigations to study whether different configurations are associated with different functional states of PrP(C).
    Veterinary Microbiology 09/2007; 123(4):358-66. DOI:10.1016/j.vetmic.2007.04.008
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    ABSTRACT: The cellular prion protein (PrP(C)) is a Cu(2+) binding protein connected to the outer cell membrane. The molecular features of the Cu(2+) binding sites have been investigated and characterized by spectroscopic experiments on PrP(C)-derived peptides and the recombinant human full-length PrP(C )(hPrP-[23-231]). The hPrP-[23-231] was loaded with (63)Cu under slightly acidic (pH 6.0) or neutral conditions. The PrP(C)/Cu(2+)-complexes were investigated by extended X-ray absorption fine structure (EXAFS), electron paramagnetic resonance (EPR), and electron nuclear double resonance (ENDOR). For comparison, peptides from the copper-binding octarepeat domain were investigated in different environments. Molecular mechanics computations were used to select sterically possible peptide/Cu(2+) structures. The simulated EPR, ENDOR, and EXAFS spectra of these structures were compared with our experimental data. For a stoichiometry of two octarepeats per copper the resulting model has a square planar four nitrogen Cu(2+) coordination. Two nitrogens belong to imidazole rings of histidine residues. Further ligands are two deprotonated backbone amide nitrogens of the adjacent glycine residues and an axial oxygen of a water molecule. Our complex model differs significantly from those previously obtained for shorter peptides. Sequence context, buffer conditions and stoichiometry of copper show marked influence on the configuration of copper binding to PrP(C).
    European Biophysics Journal 04/2007; 36(3):239-52. DOI:10.1007/s00249-006-0124-0
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    ABSTRACT: Structure and dynamics determine the function of proteins. This contribution discusses two aspects of protein dynamics, the structural fluctuation and the structural relaxation connected with conformational changes. Myoglobin and haemoglobin were investigated. To cover a wide time range different experimental techniques had to be used. Moreover, measurements in a large temperature regime were used to separate contributions from different modes of motions. Phonon assisted Mossbauer effect using synchrotron radiation allowed the study of the harmonic vibrations which have characteristic times of 1 fs to 0.6 ps. They are present in the whole temperature range from cryogenic to room temperature. With a combination of neutron structure analysis and incoherent neutron scattering it was possible to distinguish three types of hydrogen mean square displacements which are present only above a characteristic temperature T-c: These are the backbone-like (slower than about 100 ps), methyl-like (partly slower partly faster than about 100 ps) and lysine-like (faster than about 100 ps) displacements. The exceptional high energy resolution of Mossbauer absorption on Fe-57 allowed the measurement of quasi diffusive modes of molecular segments which have characteristic times slower than 1 ns and are present only above T-c. Conformational changes from the ligated to the unligated structure of myoglobin and haemoglobin were investigated by creating a metastable intermediate and observing the relaxation into the equilibrium conformation. A metastable state was obtained by X-ray irradiation. Structural relaxation was investigated as a function of time and temperature using the Mossbauer hyperfine interactions as indicator. Furthermore it was possible to measure intermediates created by photolysis of a ligand with temperature dependent X-ray structure analysis or time dependent X-ray structure analysis with the Lane technique. It was shown that the quasi diffusive structural fluctuations above T-c strongly facilitate structural relaxations. (c) 2006 Elsevier B.V. All rights reserved.
    Journal of Non-Crystalline Solids 11/2006; 352(42-49-42-49):4371-4378. DOI:10.1016/j.jnoncrysol.2006.01.106
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    ABSTRACT: Tetrapod-shaped maghemite nanocrystals are synthesized by manipulating the decomposition of iron pentacarbonyl in a ternary surfactant mixture under mild thermal conditions. Adjustment of the reaction parameters allows for the systematic tuning of both the width and the length of the tetrapod arms, which grow preferentially along the 111 easy axis direction. Such degree of control leads to modulation of the magnetic behavior of the nanocrystals, which evolves systematically as their surface magnetization phase and shape anisotropy are progressively increased.
    Nano Letters 10/2006; 6(9):1966-72. DOI:10.1021/nl061112c
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    ABSTRACT: Magnetic drug targeting employing nanoparticles as carriers is a promising cancer treatment avoiding side effects of conventional chemotherapy. We used iron oxide nanoparticles covered by starch derivatives with phosphate groups which bound mitoxantrone as chemotherapeutikum. In this letter we show that a strong magnetic field gradient at the tumour location accumulates the nanoparticles. Electron microscope investigations show that the ferrofluids can be enriched in tumour tissue and tumour cells.
    European Biophysics Journal 06/2006; 35(5):446-50. DOI:10.1007/s00249-006-0042-1
  • Fritz G Parak, Klaus Achterhold
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    ABSTRACT: Protein dynamics is studied on metmyoglobin by Mössbauer investigations with synchrotron radiation, conventional Mössbauer spectroscopy and incoherent neutron scattering. In the center of interest is the time sensitivity of mean square displacements, left angle bracketx2right-pointing angle bracket of special atoms in the protein molecule. Phonon assisted Mössbauer effect labels internal vibrations at the heme iron on a time scale from 6.5 fs to 0.65 ps. The incoherent neutron scattering yields quasi diffusive motions of side chain hydrogens on a time scale faster 100 ps. The quasi diffusive broad lines in the Mössbauer spectrum indicate slow motions of larger segments of the molecule between about 100 ns and 100 ps.
    Journal of Physics and Chemistry of Solids 12/2005; 66(12):2257-2262. DOI:10.1016/j.jpcs.2005.09.045
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    ABSTRACT: The temperature-dependent dynamics of the fully reduced and fully oxidized forms of Pseudomonas stutzeri cytochrome c4 have been studied by Mössbauer spectroscopy. Prior to the dynamic analysis, an efficient labelling strategy has been developed for the expression of highly enriched (57)Fe recombinant cytochrome c4. Subsequently, the protein has been purified to apparent homogeneity. Mössbauer measurements were recorded in the temperature range 77-240 K for both protein forms. A detailed analysis of the high quality spectra is presented. Based on the information obtained from Mössbauer spectroscopy, similarities and differences between cytochrome c4, cytochrome c and HiPIP are discussed. The obtained results reveal that (a) cytochrome c4 exists in pure low spin electronic configuration in both oxidation states in the temperature range 77-240 K, (b) the heme pocket is more relaxed in cytochrome c4 than in cytochrome c, (c) the reduced cytochrome c4 is the most flexible at low temperatures, and (d) protein specific dynamics are most distinct in the oxidized protein.
    Physical Chemistry Chemical Physics 11/2005; 7(19):3472-7. DOI:10.1039/b504955e

Publication Stats

3k Citations
326.75 Total Impact Points

Institutions

  • 1996–2009
    • Technische Universität München
      • Faculty of Physics
      München, Bavaria, Germany
  • 2005
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Anatomy Chair I
      Erlangen, Bavaria, Germany
  • 2003–2004
    • Universitätsklinikum Erlangen
      • Department of Otorhinolaryngology – Head and Neck Surgery
      Erlangen, Bavaria, Germany
  • 2001
    • Deutsches Herzzentrum München
      München, Bavaria, Germany
  • 1998
    • Technische Universität Berlin
      Berlín, Berlin, Germany
  • 1995
    • Russian Academy of Sciences
      Moskva, Moscow, Russia
  • 1991–1994
    • Johannes Gutenberg-Universität Mainz
      • Faculty of Biology
      Mayence, Rheinland-Pfalz, Germany