Elizabeth Meiering

Professor, Chemistry

Research interests: protein folding, dynamics, function, engineering and design


Biography

Professor 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, Professor 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.

Education

  • Postdoctoral Research Fellow in Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA 1992-1996
  • PhD in Biological Chemistry, University of Cambridge, England, 1992
  • BSc in Honours Chemistry, Physics Option, University of Waterloo, Canada, 1988

Elizabeth Meiering

Research

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.

Publications

ThreeFoil: folding and function of a designed, symmetric, multivalent carbohydrate binding beta-trefoil

Hisactophilin: folding and function of a model beta trefoil protein with regulated pH-dependent actin and membrane binding

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.

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