Professor of Physical Chemistry
My research focuses on the development of solid-state NMR methodology and applications of the solution and solid-state NMR to study relationships between structure, dynamics, and activity of biomolecular systems. I am particularly interested in atomic resolution characterization of solid and solid-liquid interface biological systems including, but not limited to, protein complexes, amyloid fibrils, and membrane proteins. Because the line widths in the NMR spectra in the solid-state do not depend on the size of the molecule as they do in solution, solid-state NMR offers unique opportunities to study structure and dynamics of proteins as a part of even very large assemblies. Importantly, solid-state NMR methodology can be applied to soluble and crystallisable systems but also to systems that are not soluble or that cannot be crystallised.
Membrane proteins perform crucial functions such as signaling and transport of materials across the membrane. Amyloid fibrils, a primer in self-assembling systems, are probably best known for their implication in debilitating neurodegenerative diseases such as Alzheimer’s or Parkinson’s. However, they are also involved in normal physiological processes such as biosynthesis of melanin.
Understandably, both membrane proteins and amyloid fibrils captivate not only for their intriguing biophysics but also for their medical relevance, e.g. over 50% of all drug targets act on membrane-bound receptors. However, they often lack long-range crystallinity and are insoluble and therefore, not easily amenable to detailed structural characterization by the traditional biophysical methods such as single-crystal x-ray crystallography and solution NMR. At the same, often even in the absence of long-range order, they exhibit sufficient local order to allow for a detailed atomic resolution description of both structure and dynamics by solid-state NMR.
Recently, a large fraction of the efforts in my laboratory concentrates on applications to proteins implicated in natural products biosynthesis, in particular trans-AT polyketide synthases (PKS) and polyketide synthase/non-ribosomal peptide synthase (PKS/NRPS) hybrids.
Groups at Warwick
- Department of Chemistry, University of Warwick
- 1995-1997 IB, Nordic United World College, Flekke, Norway
- 1997-1998 MISMaP, Warsaw University, Warsaw, Poland
- 1999-2003 BSc in Chemistry and Theater & Dance, Amherst College, Amherst, MA, USA
- 2002-2008 PhD (supervisor Prof. R. G. Griffin), Massachusetts Institute of Technology, Cambridge, MA, USA
- 2008-2011 Marie Curie Postdoctoral Fellow (supervisor Prof. L. Emsley), ENS de Lyon/Centre de RMN à Très Haut Champs, Lyon, France
- 2011-2015 Assistant Professor, Department of Chemistry, University of Warwick
- 2015-2019 Associate Professor, Department of Chemistry, University of Warwick
- 2019-present Professor, Department of Chemistry, University of Warwick
- BBSRC Responsive Mode, BB/R010218/1 (2018-2021): Elucidating and exploiting docking domain-mediated carrier protein recognition in natural product megasynthetases (with Greg Challis)
- ERC Starting Grant 639907 (2015-2020): Structural Dynamics of Large Protein Complexes
- NMR-led integrated structural biology of large biomolecular assemblies
- Solid-state NMR method development. Fast magic angle spinning.
- Protein dynamics
- Natural products biosynthesis
- Antibiotics and antimicrobial resistance
- Molecular modelling and simulation
CH3F2: Advanced Analytical Chemistry,
CH412: Advanced Biophysical Chemistry,
Year 3 labs
Year 1 Physical Chemistry Tutorials
CH916 Magnetic Resonance
Selected publications (for the full list with additional resources visit our group website):
- Nat. Chem. 2019, 11, 913–923. DOI: https://doi.org/10.1038/s41557-019-0335-5 | Structural Basis for Chain Release from the Enacyloxin Polyketide Synthase. Kosol, S.; A. Gallo; D. Griffiths; T. R. Valentic; J. Masschelein; M. Jenner; E. L. C. de los Santos; L. Manzi; P. K. Sydor; D. Rea; S. Zhou, V. Fülöp, N. J. Oldham, S.-C. Tsai, G. L. Challis, J. R. Lewandowski
- Nat. Chem. Biol. 2018 14(3), 270-275. DOI: 10.1038/nchembio.2549 | Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases. M. Jenner, S. Kosol, D. Griffiths, P. Prasongpholchai, L. Manzi, A.S. Barrow, J. E. Moses, N. J. Oldham, J. R. Lewandowski, G. L. Challis
- J. Am. Chem. Soc. 2017 39 (35), 12165–12174. DOI: 10.1021/jacs.7b03875 (Open Access Article) | Characterization of protein-protein interfaces in large complexes by solid state NMR solvent paramagnetic relaxation enhancements C. Öster, S. Kosol, C. Hartlmüller, J.M. Lamley, D. Iuga, A. Oss, M.-L. Org, K. Vanatalu, A. Samoson, T. Madl, J.R. Lewandowski
- Science 2015 348 (6234): 578-581. Link: http://www.sciencemag.org/content/348/6234/578 | Direct observation of hierarchical protein dynamics, Lewandowski, J.R., Halse, M.E., Blackledge, M., Emsley, L.
- Angewandte Chemie 2015 54(51), 15374–15378. DOI: 10.1002/anie.201509168 | Intermolecular interactions and protein dynamics by SSNMR Lamley, J.M., Öster, C., Stevens, R.A., Lewandowski, J.R.
- Phys. Chem. Chem. Phys. 2015, 17 (34), 21997. | Unraveling the complexity of protein backbone dynamics with combined 13C and 15N solid-state NMR relaxation measurements Lamley, J. M.; Lougher, M. J.; Sass, H. J.; Rogowski, M.; Grzesiek, S.; Lewandowski, J. R.
- J. Am. Chem. Soc. 2014 136 (48):16800–16806. Link: http://pubs.acs.org/doi/abs/10.1021/ja5069992 (Open Access) | Solid-State NMR of a Protein in a Precipitated Complex with a Full-Length Antibody, Lamley, J.M., Iuga, D., Öster, C., Sass, H.J., Rogowski, M., Oss, A., Past, J., Reinhold, A., Grzesiek, S., Samoson, A., Lewandowski, J.R.
- J. Am. Chem. Soc. 2014 136, 2833–2842. DOI: 10.1021/ja411633w | Conformational dynamics of a seven transmebrane helical protein Anabaena Sensory Rhodopsin probed by solid-state NMR. Good, DB, Wang, S, Ward, ME, Struppe, JO, Brown, LS, Lewandowski, JR, Ladizhansky, V
- J. Am. Chem. Soc. 2011 133:16762-16765. doi://10.1021/ja206815h | Site-specific Measurement of Slow Motions in Proteins. Lewandowski JR, Sass HJ, Grzesiek S, Blackledge M, Emsley
- J. Am. Chem. Soc. 2011 133: 9457-9469. doi://10.1021/ja203736z | Structural Complexity of a Composite Amyloid Fibril Lewandowski JR, van der Wel PC a, Rigney M, Grigorieff N, Griffin RG
- J. Am. Chem. Soc. 2010 132:8252-4. doi://10.1021/ja102744b | Measurement of site-specific 13C spin-lattice relaxation in a crystalline protein Lewandowski JR, Sein J, Sass HJ, Grzesiek S, Blackledge M, Emsley L
- J. Am. Chem. Soc. 2010 132:1032-40. doi://10.1021/ja906426p | High-resolution solid-state NMR structure of a 17.6 kDa protein Bertini I, Bhaumik A, De Paëpe G, Griffin RG, Lelli M, Lewandowski JR, Luchinat C
- J. Chem. Phys. 2008 129:245101. doi://10.1063/1.3036928 | Proton assisted recoupling and protein structure determination De Paëpe G, Lewandowski JR, Loquet A, Böckmann A, Griffin RG
- J. Am. Chem. Soc. 2007 129:728-9. doi://10.1021/ja0650394 | Proton assisted insensitive nuclei cross polarization Lewandowski JR, De Paëpe G, Griffin RG