My research focuses on the development of solid-state NMR methodology and applications of integrated structural biology approach with emphasis on solution and solid-state NMR and molecular dynamics simulations 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, fibrils, membrane proteins and antibiotics. 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.
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.
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/, Lyon, France
2011-2015 Assistant Professor, Department of Chemistry, 天美传媒
2015-2019 Associate Professor, Department of Chemistry, 天美传媒
2019-present Professor, Department of Chemistry, 天美传媒
Current grants:
lead (with Chris Dowson and ), EPSRC, (2025-2028): Multidisciplinary toolbox for characterising lipid II binding antibiotics
lead (with Lona Alkhalaf, Greg Challis and Matt Jenner), BBSRC, (2025-2028): Mechanisms of enoyl reductase recruitment and iterative module suppression in trans-acyltransferase polyketide synthases
lead (with Lona Alkhalaf and Greg Challis), BBSRC, (2025-2028): Elucidating and Exploiting Natural Combinatorial Biosynthesis of Hybrid Polyketide-Nonribosomal Peptide Histone Deacetylase Inhibitors
lead (with and Chris Dowson), MRC/JPIAMR, (2025-2028): Adapting Versatile Opportunities for Glycopeptide Antibiotics against Drug-Resistant Organisms ( AVOGADRO)
co-lead (lead Richard Napier), BBSRC, (2025-2028): The auxin degron: a necessary twist for plant life?
co-lead, EPSRC, (2024-2028): Pushing the Limits of High-Field Solid-State NMR Technology: Enhancing Applications to Advanced Materials, the Life Sciences and Pharmaceuticals
co-lead, EPSRC/BBSRC, (2023-2028): NMR at 1.2 GHz: A World-Leading UK Facility to Deliver Advances in Biology, Chemistry, and Materials Science
Previous grants:
lead, BBSRC Responsive Mode, BB/W003171/1 (2021-2024): Illuminating and exploiting programmed O-methylation in trans-AT polyketide synthases (with Greg Challis)
lead, BBSRC ALERT21, BB/W020297/1 (2022-2023): Enabling new characterisation methods for dynamic systems through the upgrade of 700 MHz solution NMR spectrometer
NMR-led integrated structural biology of large biomolecular assemblies
Solid-state NMR method development. Fast magic angle spinning.
Natural products biosynthesis
Protein dynamics
Antibiotics and antimicrobial resistance
Molecular modelling and simulation\
Bioinformatics
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Selected publications (for the full list with additional resources visit our group website):
Nat. Chem. 2019, 11, 913鈥�923. DOI: | Structural Basis for Chain Release from the Enacyloxin Polyketide Synthase. S. 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. F眉l枚p, N. J. Oldham, S.-C. Tsai, G. L. Challis, J. R. Lewandowski
Nat. Chem. Biol. 2018 14(3), 270-275. DOI: | Mechanism of intersubunit ketosynthase鈥揹ehydratase interaction in polyketide synthases. M. Jenner, S. Kosol, D. Griffiths, P. Prasongpholchai, L. Manzi, A.S. Barrow, J. E. Moses, , J. R. Lewandowski, G. L. Challis
J. Am. Chem. Soc. 2017 39 (35), 12165鈥�12174. DOI: | Characterization of protein-protein interfaces in large complexes by solid state NMR solvent paramagnetic relaxation enhancements C. 脰ster, S. Kosol, C. Hartlm眉ller, 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: | Direct observation of hierarchical protein dynamics, Lewandowski, J.R., Halse, M.E., Blackledge, M., Emsley, L.
Angewandte Chemie 2015 54(51), 15374鈥�15378. DOI: | Intermolecular interactions and protein dynamics by SSNMR Lamley, J.M., 脰ster, 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鈥�16806. Link: | Solid-State NMR of a Protein in a Precipitated Complex with a Full-Length Antibody, Lamley, J.M., Iuga, D., 脰ster, 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鈥�2842. DOI: | 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. | 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. | 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. | 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. | High-resolution solid-state NMR structure of a 17.6 kDa protein Bertini I, Bhaumik A, De Pa毛pe G, Griffin RG, Lelli M, Lewandowski JR, Luchinat C
J. Chem. Phys. 2008 129:245101. | Proton assisted recoupling and protein structure determination De Pa毛pe G, Lewandowski JR, Loquet A, B枚ckmann A, Griffin RG
J. Am. Chem. Soc. 2007 129:728-9. | Proton assisted insensitive nuclei cross polarization Lewandowski JR, De Pa毛pe G, Griffin RG
