Contact Waterloo Institute for Nanotechnology
Mike & Ophelia Lazaridis Quantum-Nano Centre, Room 3606
University of Waterloo
200 University Ave. W.
Waterloo, ON. N2L 3G1
+1 519 888 4567, ext.38654
Research interests: protein folding, dynamics, function, engineering and design
Dr. Meiering grew up in Guelph, Ontario and Bocholt, Germany. She graduated with a BSc degree in Honours Chemistry, Physics Option in 1988 from the University of Waterloo. She completed her PhD in 1992 at the University of Cambridge with her thesis on the influence of active site residues on the folding and function of barnase, with supervisor Professor Sir Alan Fersht in the Department of Chemistry. She then worked as a postdoctoral research fellow at Harvard Medical School in the Department of Biological Chemistry and Molecular Pharmacology. Her postdoctoral research was on the activity and drug binding of dihydrofolate reductase analyzed by multidimensional heteronuclear NMR in the group of Professor Gerhard Wagner.
In 1996, Dr. Meiering joined the faculty of the Department of Chemistry at the University of Waterloo, where she currently holds the position of Full Professor. She won a John Charles Polanyi Award and a University Research Chair. Her professional activities include serving on the Editorial Board for Protein Engineering Design and Selection, the ALS Society of Canada Scientific Advisory Board, CIHR Grant Review Committee, NIH Grant Review Panel, and a wide range of other internal and external committees and roles, including as Associate Dean of Graduate Studies and Associate Director of the Centre for Bioengineering and Biotechnology University of Waterloo, as well as Chair of the Proteins Gordon Research Conference and Executive Council Member of The Protein Society.
- 1992-1996 Postdoctoral Research Fellow in Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA
- 1992 PhD in Biological Chemistry, University of Cambridge, England
- 1988 BSc in Honours Chemistry, Physics Option, University of Waterloo, Canada
Professor Meiering’s research group is elucidating how the primary amino acid sequence of a protein determines its folding and function. Knowledge of the molecular mechanisms governing protein folding, dynamics and function is essential for understanding natural proteins, misfolding and toxicity of variant proteins in disease and biotechnology, and engineering or designing proteins for a great, and barely tapped, range of modern biotechnological and medical applications.
They use a multidisciplinary approach integrating complementary experimental and modelling methods, to produce, engineer, and analyze recombinant protein variants in bacteria (E. coli) using biochemical and biophysical techniques, such as: differential scanning and isothermal titration calorimetry (DSC, ITC), multi-dimensional heteronuclear NMR spectroscopy, optical spectroscopies (fluorescence, CD, FTIR), light scattering, stopped-flow rapid mixing, atomic force microscopy, and computational modelling (bioinformatics, Rosetta, molecular dynamics). They analyze diverse proteins of biological, biotechnological and medical importance.
Current projects include:
- Hisactophilin: folding and function of a model beta trefoil protein with regulated pH-dependent actin- and membrane-binding
- ThreeFoil: folding and function of a designed, symmetric, multivalent carbohydrate binding beta-trefoil protein
- Adnectins: stability and solubility of engineered target binding protein biologics
- Human Superoxide Dismutase: protein folding and aggregation toxicity in disease
A more in depth description of current research projects can be found on the Meiering group website Protein Folding Laboratory.
ThreeFoil: folding and function of a designed, symmetric, multivalent carbohydrate binding beta-trefoil
- Broom, A., Ma, S.M., Xia, K., Rafalia, H., Trainor, K., Colon, W., Gosavi, S., and Meiering, E.M.* Designed protein reveals structural determinants of extreme kinetic stability. Proceedings of the National Academy of Sciences USA 112, 14605-10 (2015). (pdf)
- Broom, A., Doxey, A.C., Lobsanov, Y.D., Berthin, L.G., Rose, D.R., Howell, P.L., McConkey, B.J.*, and Meiering, E.M.* Modular evolution and the origins of symmetry: Reconstruction of a three-fold symmetric globular protein. Structure 20, 161-171 (2012). (pdf)
Hisactophilin: folding and function of a model beta trefoil protein with regulated pH-dependent actin and membrane binding
- Shental-Bechor, D., Smith, M.T.J., Mackenzie, D., Broom, A., Marcovitz, A., Ghashut, F., Go, C., Bralha, F., Meiering, E.M.*, and Levy, Y.* Nonnative interactions regulate folding and switching of myristoylated protein. Proceedings of the National Academy of Sciences USA109, 17839-44 (2012). (pdf)
- Smith, M.T.J., Meissner, J., Esmonde, S., Wong, H.J., and Meiering, E.M.* Energetics and mechanisms of folding and flipping the myristoyl switch in the beta-trefoil protein, hisactophilin. Proceedings of the National Academy of Sciences USA 107, 20952-20957 (2010) (pdf).
Adnectins: stability and solubility of engineered target binding protein biologics
- Trainor, K., Gingras, Z., Shillingford, C., Malakian, H., Gosselin, M., Lipovsek, D., and Meiering, E.M.* Ensemble Modeling and intracellular aggregation of an engineered immunoglobulin-like domain. J. Mol. Biol. 428, 1365-74 (2016) (pdf)
Human Superoxide Dismutase: protein folding and aggregation toxicity in ALS
- Broom, H.R., Rumfeldt, J.A.O., and Meiering, E.M.* Many roads lead to Rome? Multiple modes of Cu,Zn superoxide dismutase destabilization, misfolding and aggregation in amyotrophic lateral sclerosis. Essays in Biochemistry 56, 149-65 (2014) (pdf).
- Sekhar, A.*, Rumfeldt, J.A., Broom, H.R., Doyle, C.M., Bouvignies, G., Meiering, E.M.*, and Kay, L.E.* Thermal fluctuations of immature SOD1 lead to separate folding and misfolding pathways. eLife 4, e07296/33pgs (2015) (pdf).
- Vassall, K.A., Stubbs, H.R., Primmer, H.A., Tong, M.S., Sullivan, S.M., Sobering, R., Srinivasan, S., Briere, L.A.K., Dunn, S.D., Colon, W., and Meiering, E.M.* Decreased stability and increased formation of soluble aggregates by immature superoxide dismutase do not account for disease severity in ALS. Proceedings of the National Academy of Sciences USA 108, 2210-2215 (2011) (pdf).
Please see the Protein Folding Laboratory website for further information on the Meiering group’s research and publications.