Dr Eric J. M. Lang

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I am a Postdoctoral Research Associate funded by BrisSynBio (the Bristol Synthetic Biology Research Centre, part of the University of Bristol) and working on a variety of synthetic biology problems using molecular modelling methods, including all atom molecular dynamics (MD) simulations, constant pH MD simulations, quantum mechanical calculations, hybrid QM/MM approaches, homology modelling and molecular docking.sol_geom1_3.2

I am particularly interested in understanding enzyme catalysis, substrate recognition and allosteric regulation in proteins. De novo proteins like the water soluble α-helical barrels designed and synthesised in the group of Professor Derek Woolfson, provide an ideal playground to understand these fundamental questions. Because of their relative simplicity, the study of these engineered proteins reveals valuable information directly transferable to natural proteins and enable to confront the results of the simulations with experimental data.

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Prior to join the Mulholland group at the University of Bristol, I obtained, in 2016, a PhD in chemistry from the University of Canterbury in New Zealand under the supervision of Professor Emily J. Parker. There I worked on providing new insights into the understanding of allostery by studying computationally allosteric regulation in the metabolic enzyme 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) which catalyses the first committed step in the biosynthesis of aromatic amino acids. Not only is DAH7PS a promising antimicrobial drug target, owing to its presence in microorganisms but not in animals, but also, the unique variety of allosteric regulation mechanisms found in this protein family makes it the ideal target to study allostery. pka_shift_residues6

I obtained an Engineer’s degree in chemistry from the National Graduate School of Chemistry of Mulhouse (Ecole Nationale Supérieure de Chimie de Mulhouse), France with a specialisation in Organic and Bioorganic Chemistry and a Master’s degree in Organic and Macromolecular Synthesis from the University of Haute Alsace, France in 2005. Throughout and following my studies, I worked as a medicinal chemist for GSK in Harlow, UK; the Laboratory of Organic and Bioorganic Chemistry at the University of Haute Alsace in Mulhouse, France; University of Strasbourg in Strasbourg, France and Novartis in Basel, Switzerland over a total period of 3 years. I was mainly involved in the synthesis of lead compounds and on the determination of the structure–activity relationship. In 2007, I completed a Master’s degree in Innovation and Technology Management at the Toulouse Business School, France and subsequently joined Novasep in Pompey, France as Technical Marketing Manager for the Synthetic Molecules business of the company. There, I was in charge of market research as well as strategic and operational marketing for Novasep’s offering for the pharmaceutical industry, before going back to academic research in 2012.tma19_top_0ns

Publications:

Rhys, G. G.; Wood, C. W.; Lang, E. J. M.; Mulholland, A. J.; Brady, R. L.; Thomson, A. R.; Woolfson, D. N., Maintaining and breaking symmetry in homomeric coiled-coil assemblies. Nature communications 2018, 9 (1), 4132

Sterritt, O. W.; Lang, E. J. M.; Kessans, S. A.; Ryan, T. M.; Demeler, B.; Jameson, G. B.; Parker, E. J., Structural and functional characterisation of the entry point to pyocyanin biosynthesis in Pseudomonas aeruginosa defines a new 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase subclass. Bioscience Reports 2018, 38 (5), BSR20181605.

Thomas, F.; Dawson, W. M.; Lang, E. J. M.; Burton, A. J.; Bartlett, G. J.; Rhys, G. G.; Mulholland, A. J.; Woolfson, D. N., De Novo-Designed α-Helical Barrels as Receptors for Small Molecules. ACS Synthetic Biology 2018, 7 (7), 1808-1816.

Lang, E. J. M.; Mulholland A. J., 3.04 Molecular Dynamics, Quantum Mechanics and Combined Quantum Mechanics / Molecular Mechanics Methods for Drug Discovery and Development. In Comprehensive Medicinal Chemistry III, volume 3, Chackalamannil, S.; Rotella, D.; Ward, S., Eds. Elsevier: Amsterdam, 2017, 51-66.

Nazmi, A. R.; Lang, E. J. M.; Bai, Y.; Allison, T. M.; Othman, M.; Panjikar, S.; Arcus, V. L.; Parker, E. J., Interdomain Conformational Changes Provide Allosteric Regulation en Route to Chorismate. Journal of Biological Chemistry 2016, 291 (42), 21836-21847.

Lang, E. J. M.; Heyes, L. C.; Jameson, G. B.; Parker, E. J., Calculated pKa Variations Expose Dynamic Allosteric Communication Networks. Journal of the American Chemical Society 2016, 138 (6), 2036–2045.

Lang, E. J. M.; Cross, P. J.; Mittelstadt, G.; Jameson, G. B.; Parker, E. J., Allosteric ACTion: the varied ACT domains regulating enzymes of amino-acid metabolism. Current Opinion in Structural Biology 2014, 29, 102-111.

Bléhaut, J.; Franco, P.; Zhang, T.; Lang, E.; Valéry, E.; Marcoux, J.-F., 9.17 Industrial Applications of Chiral Chromatography. In Comprehensive Chirality, Carreira, E. M.; Hisashi, Y., Eds. Elsevier: Amsterdam, 2012; 400-456.

Lang, E.; Valéry, E.; Ludemann-Hombourger, O.; Majewski, W.; Bléhaut, J., Preparative and Industrial Scale Chromatography: Green and Integrated Processes. In Green Chemistry in the Pharmaceutical Industry, Dunn, P. J.; Wells, A. S.; Williams, M. T., Eds. Wiley-VCH Verlag GmbH & Co. KGaA: 2010; 243-268.

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