Summary: My research interests include structural and biophysical characterization of biomolecules. From peptides to proteins, nucleic acids and metabolites, these molecules are integral to life and the maintenance of living systems. The thematic focus of my research is studying the interplay between these biomolecules in the cell and in the extracellular matrix. I routinely use biomolecular nuclear magnetic resonance (bioNMR), small angle X-ray scattering, circular dichroism, and isothermal titration calorimetry to characterize these interacting systems. When working with large assemblies of molecules, it is often difficult to collect high-quality data. To overcome these technical challenges, we use sparse experimental data combined with molecular modeling to build knowledge-based models of multicomponent biomolecular systems.
- Warner L. R., Gatzeva-Topalova P.Z., Doerner P.A., Pardi A., Sousa M.C. (2017) Flexibility in the Periplasmic Domain of BamA Is Important for Function. Structure, Jan 3;25(1):94-106.
- Hennig, J., Warner, L. R., Simon, B., Geerlof, A., Mackereth, C. D., & Sattler, M. (2015). Structural Analysis of Protein-RNA Complexes in Solution Using NMR Paramagnetic Relaxation Enhancements. Methods in Enzymology, 558, 333–62.
- Huang, J. R., Warner, L. R., Sanchez, C., Gabel, F., Madl, T., Mackereth, C. D., Blackledge, M. (2014). Transient electrostatic interactions dominate the conformational equilibrium sampled by multidomain splicing factor U2AF65: A combined NMR and SAXS study. JACS, 136, 7068–7076.
- Warner, L. R., Schilling, F., Gershenzon, N. I., Skinner, T. E., Sattler, M., & Glaser, S. J. (2014). Next-generation heteronuclear decoupling for high-field biomolecular NMR spectroscopy. Angewandte Chemie – International Edition, 53(17), 4475–4479.
- Xiao, Y., Lee, T., Latham, M. P., Warner, L. R., Tanimoto, A., Pardi, A., & Ahn, N. G. (2014). Phosphorylation releases constraints to domain motion in ERK2. PNAS, 111(7), 2506–2511.
- Warner, L. R., Varga, K., Lange, O. F., Baker, S. L., Baker, D., Sousa, M. C., & Pardi, A. (2011). Structure of the BamC two-domain protein obtained by Rosetta with a limited NMR data set. JMB, 411(1), 83–95.
Minimum Classes: General Chemistry
Projects: We have three projects in the lab that are open to summer fellows. 1) Defining the molecular interactions that govern interactions between the protein LARP6 and collagen mRNA and determining how these and auxiliary interactions regulate mRNA trafficking in cells. 2) Structural characterization of small molecular inhibitors bound to cancer and heart disease-related drug target proteins. 3) Following carbon metabolic flux analysis in anaerobic bacteria using in-cell 13C NMR tracer analysis.
Work in the Warner lab will include training on protein expression and purification techniques using an E. coli platform and incorporating stable isotope enrichment, verification of the quality and quantity of proteins produced using standard laboratory protocols; SDS gel electrophoresis, dot-blot assays, UV-VIS spectroscopy, Western Blot analysis, etc. The skillsets gained while working on these projects translate well between research and industrial applications. In addition, you will learn at least one advanced technique as it applies to your project, either nuclear magnetic resonance (NMR), analytical ultracentrifugation (AUC), circular dichroism (CD), or isothermal titration calorimetry (ITC).