dr. M.H. (Markus) Weingarth
M.H.Weingarth@uu.nl
Gegenereerd op 2017-11-18 18:39:51


Profile

Biomolecular solid state NMR

 

Research interests

  • membrane proteins (especially ion channels)
  • antibiotics
  • self-assembling peptides
  • methods development (especially proton-detection)

 

Research Group

Our research focuses on the development of modern sensitivity-enhanced solid-state NMR methods and their integration with computational techniques. For example, we develop proton-detected methods that can strongly accelerate solid-state NMR experiments and thereby enable us to study very challenging biomolecules such as proteins in native cell membranes.

We use our methods to study pharmaceutically important systems such as antibotics, nanoscale drug-vectors, and ion channels. We strive to study these complex biological assemblies at truly physiological conditions and at the atomic level.

For further information, please visit the group homepage!

 
Group Picture
 
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Curriculum vitae Download PDF

 

CV

Date of birth     02. June 1982 (in Mainz, Germany)
2002/7                Biochemistry studies, University of Greifswald
2007                   PhD student, EPF Lausanne, with G. Bodenhausen              
2007/10              PhD fellow, ENS Paris (rue d'Ulm), with G. Bodenhausen         
2011                   FEBS fellow, Utrecht University, with M. Baldus
2013                   VENI fellow, Utrecht University, with M. Baldus
2015                   Group leader, Assitant Professor, Utrecht University

 

Awards

2004                    Award of the German chemical society for the best Pre-Diploma
2006                    Diploma “mit Auszeichnung” (with distinction), all grades 1.0
2007/10               PhD Fellowship of the French Research Ministry                                                
2011/13                Federation of European Biochemical Societies (FEBS) Long-term Fellowship     
2012                     IUBMB & FEBS Young Scientist Program Fellowship         
2012/15               VENI fellowship of the Netherlands Organization of Scientific Research (NWO)  
2014                    FEBS Distinguished Young Investigator Award (only laureate in 2014)
2015/20               VIDI fellowship of the Netherlands Organization of Scientific Research (NWO)  

 

NWO VIDI Laureate 2015 
JACS cover
 

I received the 'Dinstiguished Young Investigator Award' of the Federations of European Biochemical Societies (FEBS) in 2014. See here for the feature in the FEBS news. 

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Selected Recent Publications

A. Visscher, K.M.,  Medeiros-Silva, J. Mance, D., Rodrigues, J.P.G.L.M., Daniëls, M., Bonvin, A.M.J.J., Baldus, M., Weingarth. M. (2017) Angew. Chem., 56, 13222, Supramolecular organization and functional implications of K+ channel clusters in membranes  (open access) Frontispiece

B. Medeiros-Silva, J., Mance, D., Daniels, M., S. Jekhmane, Houben, K., Baldus, M., Weingarth. M. (2016) Angew. Chem., 55, 13606, 1H- detected solid-state NMR studies of water-inaccessible proteins in vitro and in situ   (open access)

C. Mance, D., Sinnige, T., Kaplan, M., Narasimhan, S., Danïels, M., Houben, K., Baldus, M., Weingarth. M. (2015) Angew. Chem., 54, 15799, An efficient labelling approach to harvest backbone and side chain protons in 1H-detected solid-state NMR  (open access)

Selected as NWO Chemical Highlight (in Dutch)

D. Rad Malekshahi, M., Visscher. K.M., Rodrigues J.P.G.L.M., de Vries, R., Hennink, W.E.,  Baldus, M., Bonvin A.M.J.J., Mastrobattista E., Weingarth. M. (2015) J. Am. Chem. Soc., 137, 7775, The supramolecular organization of a peptide based nanocarrier at high molecular detail 

E. Sinnige, T., Daniels, M., Baldus, M., Weingarth. M. (2014) J. Am. Chem. Soc., 136, 4452, Proton clouds to measure non-exchangable sidechain protons in solid-state NMR

This article featured on the cover of JACS and was the selected as highlight

 

 

Publications

32. Tikhonova, E., Hariharan, P., Medeiros-Silva, J., Bogdanov, M.V., Dowhan, W., Weingarth, M.,* Guan, L.,* (2017) under review, Functional lipid-protein interactions in a melibiose transporter revealed by solid-state NMR spectroscopy and lipid-engineered bacteria

31. Visscher, K.M.,  Medeiros-Silva, J. Mance, D., Rodrigues, J.P.G.L.M., Daniëls, M., Bonvin, A.M.J.J., Baldus, M., Weingarth. M. (2017) Angew. Chem., 56, 13222, Supramolecular organization and functional implications of K+ channel clusters in membranes  (open access) Frontispiece

30. Medeiros-Silva, J., S. Jekhmane, Baldus, M.,Weingarth. M. (2017) Solid State Nucl. Magn. Reson., in press, 1Hydrogen bond strength in membrane proteins by time-resolved 1H-detected solid-state NMR and MD simulations  invited article, special issue: Ultra-fast MAS  (open access)

29. Medeiros-Silva, J., Mance, D., Daniels, M., S. Jekhmane, Houben, K., Baldus, M., Weingarth. M. (2016) Angew. Chem., 55, 13606, 1H- detected solid-state NMR studies of water-inaccessible proteins in vitro and in situ   (open access)

28. Chung, S., Angelici, C., Hinterding, S.O.M., Weingarth. M., Baldus, M., Houben, K., Weckhuysen, B.M., Bruijnincx, P.C.A. (2016) ACS Catal., 6, 4034, On the role of magnesium silicates in wet-kneaded silica-magnesia catalysts for the Lebedev ethanol-to-butadiene process    (open access)

27. Mance, D., Sinnige, T., Kaplan, M., Narasimhan, S., Danïels, M., Houben, K., Baldus, M., Weingarth. M. (2015) Angew. Chem., 54, 15799, An efficient labelling approach to harvest backbone and side chain protons in 1H-detected solid-state NMR   (open access)

26. Jantschke, A., Koers, E., Mance, D., Weingarth. M., Brunner, E., Baldus, M. (2015) Angew. Chem., 54, 15069, Insight into the Supramolecular Architecture of Intact Diatom Biosilica Using a DNP-Solid-State NMR-Based Approach

25. Rad Malekshahi, M., Visscher. K.M., Rodrigues J.P.G.L.M., de Vries, R., Hennink, W.E.,  Baldus, M., Bonvin A.M.J.J., Mastrobattista E., Weingarth. M. (2015) J. Am. Chem. Soc., 137, 7775, The supramolecular organization of a peptide based nanocarrier at high molecular detail 

24. van der Cruijsen, E., Koers, E., Sauvée, C., Hulse, R.E., Weingarth. M., Ouari, O., Perozo, E., Tordo, T., Baldus, M. (2015) Chemistry—A European Journal, 21, 12971,  Biomolecular DNP- supported NMR spectroscopy using sitedirected spin labeling

23. van Zandvoort, I., Koers, E.J.,Weingarth. M., Bruijnincx, P.C.A. Baldus, M., Weckhuysen, B.M (2015) Green Chemistry, 17, 4383, Structural Characterization of 13C-Enriched Humins and Alkali-treated 13C Humins by 2D Solid-state NMR

22. Sinnige, T., Weingarth. M., Daniels, M., Boelens, R.,  Bonvin, A.M.J.J., Houben, K., Baldus, M.,  (2015) Structure, 23, 1317, Conformational plasticity of the POTRA 5 domain in the outer membrane protein assembly factor BamA

21. Koers, E., van der Cruijsen, E., Rosay, M., Weingarth. M., Prokofyev, A., Sauvée, C., Ouari, O., Pongs, O., Tordo, P., Maas, W., Baldus, M. (2014) J. Biomol. NMR, 60, 157.  NMR-based Structural Biology enhanced by Dynamic Nuclear Polarization at high magnetic field

20. Sinnige, T., Weingarth. M. Renault, M., Baker, L., Tommassen, J., Baldus, M. (2014) J. Mol. Bio., 426, 2009. Solid-state NMR studies of full-length BamA in lipid bilayers suggest limited overall POTRA mobility

19. Sinnige, T., Daniels, M., Baldus, M.,Weingarth. M. (2014) J. Am. Chem. Soc., 136, 4452. Proton clouds to measure non-exchangable sidechain protons in solid-state NMR

Cover Article

Comment

18. Weingarth. M.* van der Cruijsen, E., Ostmeyer, J., Lievestro, S. Roux, B., Baldus, M.,* (2014) J. Am. Chem. Soc., 136, 2000, Quantitative analysis of the water occupancy around the selectivity filter of a K+ channel in different gating modes *co-corresponding authors.

17. Koers, E. J., Lopez-Deber, M. P., Weingarth. M. Nand, D.,  Hickman, D. T., MlakiNdao, D., Pfeifer, A., Muhs, A., Baldus, M. (2013) Angew. Chem., 52, 10905. Dynamic Nuclear Polarization NMR reveals multiple conformations in lipid-anchored Peptide Vaccines

16. van der Cruijsen, E., Nand, D., Weingarth. M. Prokofyev, A., Hornig, S., Cukkemane, A., Bonvin, A. MMJ, Becker, S., Hulse, R. E., Perozo, E., Pongs, O., Baldus, M. (2013) Proc. Natl. Acad. Sci. USA, 110, 13008. The importance of the lipid-pore loop interface for potassium channel structure and function

15. Weingarth. M., Baldus, M. (2013) Acc. Chem. Res., 46, 2037. Solid-State NMR-Based Approaches for Supramolecular Structure Elucidation

14. Weingarth. M., Prokovyef, A., van der Cruijsen, E., Nand, D., Bonvin, A., Pongs, O., Baldus, M.  (2013), J. Am. Chem. Soc., 135, 10. Structural determinants of specific lipid binding to potassium channels

13. Weingarth. M., Ader, C., Melqiond, A., Nand, D., Pongs, O., Becker, S., Bonvin, A., Baldus, M. (2012), Biophys. J.,  103, 29. Supramolecular structure of membrane-associated polypeptides by combining solid-state NMR and molecular dynamics simulations

12. Cukkemane, A., Nand, D., Gradmann, S., Weingarth. M., Baldus, M. (2012) Biomol. NMR Assign. 6, 225. Solid-state NMR [13C,15N] resonance assignments of the nucleotide-binding domain of a bacterial cyclic nucleotide-gated channel

11. Weingarth. M. Trebosc, J., Amoureux, J.P., Bodenhausen, G., Tekely, P. (2011) Solid State Nucl. Magn. Reson. 40, 21. Efficiency at high spinning frequencies of heteronuclear decoupling methods designed to quench rotary resonance

10. Weingarth. M. Masuda, Y., Takegoshi, Bodenhausen, G., Tekely, P. (2011) J. Biol. NMR 50, 129.  Sensitive (13)C- 13)C correlation spectra of amyloid fibrils at very high spinning frequencies and magnetic fields

9. Weingarth. M. Bodenhausen, G. and Tekely, P. (2010) Chem. Phys. Lett. 502, 259. Probing the quenching of rotary resonance by PISSARRO decoupling

8. Weingarth. M. Bodenhausen, G., Tekely, P. (2010) Chem. Phys. Lett. 488, 10. Selected as Editor’s choice article. Broadband magnetization transfer using moderate radio-frequency fields for NMR with very high static fields and spinning speeds

7. Weingarth. M. Tekely, P., Brüschweiler, R., Bodenhausen, G. (2010) Chem. Comm. 46, 952. Selected for Highlights in Chemical Biology Improving the quality of 2D solid-state NMR spectra of microcrystalline proteins by covariance analysis

6. Weingarth. M. Bodenhausen, G., Tekely, P. (2009) J. Am. Chem. Soc. 131, 13937. Broadband carbon-13 correlation spectra of microcrystalline proteins in very high magnetic fields

5. Weingarth. M. Bodenhausen, G., Tekely, P. (2009) J. Magn. Reson. 199, 238. Low-power decoupling at high spinning frequencies in high static fields

4. Weingarth. M. Demco, D., Bodenhausen, G., Tekely, P. (2009) Chem. Phys. Lett. 469, 342. Improved magnetization transfer in solid-state NMR with fast magic angle spinning

3. Rettig, M.*, Weingarth. M.*, Langel, W., Kamal, A., Kumar, P.P., Weisz, K. (2009) Biochemistry 48, 12223. *co-first authors Solution structure of a covalently bound pyrrolo[2,1-c][1,4]benzodiazepine-benzimidazole hybrid to a 10mer DNA duplex

2. Weingarth. M. Tekely, P., Bodenhausen, G. (2008) Chem. Phys. Lett. 466, 247. Efficient heteronuclear decoupling by quenching rotary resonance in solid-state NMR.

1. Weingarth. M., Raouafi, N., Jouvelet, B.,Duma, L.,Bodenhausen, G., Boujlel, K., Schöllhorn, B., Tekely, P. (2008) Chem. Comm. 45, 5981. Revealing molecular self-assembly and geometry of non-covalent halogen bonding by solid-state NMR spectroscopy

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For further information, please visit the group homepage!

I. Solid-state NMR method development  -  1H detection 

Due to their high gyromatic ratio, the detection of protons can much increase NMR spectral sensitivity compared to the detection of heteronuclei such as carbon or nitrogen. The advent of 1H-detection in biological solid-state NMR spectroscopy has indeed marked a milestone and it can be forseen that this technique will become the new standard to study solid proteins. However, to assign aliphatic side chain protons and to harness them for structural studies are, as yet, significant challenges to solid-state NMR spectroscopists. These a critical roadblocks to the use of 1H-dectection to study proteins, given that side chains are mandatory to understand protein structure and function. 

We have recently introduced a new labeling approach - dubbed Fractional deuteration - for 1H-detected solid-state that gives access to very-well resolved backbone and side-chain protons of proteins (see Angew. Chem. 2015). In fact, for non-microcrystalline proteins such as membrane proteins or fibrils, this approach is much more benefitial than the traditional perdeuteration approach, as we showed on the membrane-embedded ion channel KcsA. More will follow soon!

   Fractional deuteration

 

 

Proton cloud labelling: Furthermore, we have demonstrated that selective labeling of proteins with protonated amino acids embedded in a perdeuterated matrix, dubbed ‘proton clouds’, provides general access to long-range contacts between nonexchangeable side chain protons in 1H-detected solid-state NMR (see Weingarth et al. JACS 2014). This article was selected for the Cover of JACS (see also Comment). 

   Proton Clouds

 

 

Proton detection in fully protonated membrane proteins: Another issue that we have tackled is that trans-membrane regions of proteins are usually inaccessible to reprotonation protocols, which is a dilemma for 1H-detection of exchangeable backbone protons, since functionally important sites are often deeply buried in lipid-shielded protein cores. We have recently demonstrated for the first time the feasability of proton detection of fully protonated membrane proteins on the example of an ion channel (see Weingarth et al. JACS 2014) - which abolishes the necessity to reprotonate exchangeable protons altogether.

 

 

II. Supramolecular Structure of membrane proteins 

Membrane proteins act in dynamic interplay with their membrane environment, which is hitherto poorly understood at a molecular level, let alone at atomic resolution (see our recent review, Weingarth et al. 2013 Acc. Chem.) The core techniques that I use to study membrane proteins are solid-state NMR and molecular dynamics simulations. I am especially interested to understand how generic and specific properties of lipids shape function and structure of membrane proteins like ions channels or transporters (see, for example some of my recent articles Weingarth et al. 2013 JACS ; Koers et al. 2013 Angew. Chem. ; van der Cruijsen et al. 2013 PNAS - the latter two articles give you a taste of my MD simulations).

I am interested to acquire the complete picture, i.e., the supramolecular structure of membrane proteins. I have recently developed approaches to study other determinates of membrane protein function and structure like rigid water (see Weingarth et al. 2014 JACS, which is based on this elegant study of our collaborators) or membrane protein - membrane protein interactions.

Supramolecular interactions
 
 
 

III. Peptide-based nanomaterials at high-resolution 

In collaboration with Utrecht Pharmacy department, we could recently present an approach (Rad Malekshahi et al., 2015, JACS) which allows studying peptide-based nanovesicles at physiological conditions and at high-resolution, an important advance towards the tailoring of such materials for medial applications.

 
Nanovesicles self-assembled from amphiphilic peptides are promising candidates for applications in drug delivery. However, complete high-resolution data on the local and supramolecular organization of such materials has been elusive thus far, which is a substantial obstacle to their rational design. In the absence of precise information, nanovesicles built of amphiphilic ‘lipid-like’ peptides are generally assumed to resemble liposomes that are organized from bilayers of peptides with a tail-to-tail ordering. We have recently reported the local and global organization of the multi-megadalton SA2 peptide-based nanocarrier at unprecedented detail and at close-to physiological conditions. By integrating a multitude of experimental techniques (solid-state NMR, AFM, SLS, DLS, FT-IR, CD) with large- and multi-scale MD simulations, we could show that SA2 peptide nanocarriers are built of interdigitated antiparallel β-sheets, which bear little resemblance to phospholipid liposomes. Our high-resolution study provides a number of potential leads to improve and tune the biophysical properties of the nanocarrier and our approach may be of general utility to investigate peptide-based nanomaterials at high-resolution and at physiological conditions.

 

SA2

 

 

 

 

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Additional functions and activities

none

Gegenereerd op 2017-11-18 18:39:51
Full name
dr. M.H. Weingarth Contact details

Visiting address: 
Nicolaas Bloembergengebouw, room 1.06
Padualaan 8, 3584 CH Utrecht
Accessible via Kruyt Building -> first floor -> bridge to Sjoerd Groenman Building
See
https://www.uu.nl/en/research/nmr/contact/route

Postal address:
Universiteit Utrecht, NMR
Padualaan 8, 3584 CH Utrecht


Phone
 (direct)
: +31 30 253 9932

Phone (secr): +31 30 253 2652

Gegenereerd op 2017-11-18 18:39:51
Last updated 13.11.2017