Department of Molecular and Cellular Biology Faculty . Dr. Chris Whitfield

Email: cwhitfie@uoguelph.ca
Office: SSC 4245
Ext: 53361
Lab: SSC 4202
Ext: 54710

The Whitfield Lab

Profile

My interest in microbiology began as an undergraduate at the University of Newcastle-on-Tyne (UK). I had planned to pursue a degree in another discipline and took a first-year course in microbiology, largely to see what it was all about. I became fascinated by bacterial systems and their contributions to our understanding of many of the critical fundamental questions in biology. I ended up switching my major and developed an interest that still drives my research and teaching today. I was first introduced to the area of prokaryotic glycobiology in my Ph.D. work at the University of Edinburgh, and expanded my knowledge of this broad field through postdoctoral fellowships at the University of California at Davis and the University of Calgary. Since joining the University of Guelph, my research group’s focus has been on the structure and assembly of bacterial cell surfaces. This has its roots in those postdoctoral studies but now involves a variety of different membrane trafficking systems. With the ever-advancing sophistication of experimental methods we are now able to address key scientific questions at an unprecedented level of molecular detail. There are always further important questions to ask and our interest and continued progress are now enhanced by the integration of multidisciplinary approaches, and valued international collaborations.

Education

B.Sc. University of Newcastle-upon-Tyne
Ph.D. University of Edinburgh

Research

Research in my laboratory is focused on the architecture and assembly of the cell surfaces of pathogenic bacteria. Complex molecular machines coordinate the synthesis and export of cell-surface macromolecules and our goal is to understand their structure and function. This represents a fascinating challenge for experimental research and involves the application of a range of experimental strategies that span the disciplines of biochemistry, microbiology, molecular biology, and structural biology. The systems being investigated are of fundamental importance in understanding the physiology and pathogenesis of bacteria and they may yield new therapeutic strategies for intervention in bacterial infections.

Current areas of emphasis are:

  1. Structure and function of multi-enzyme complexes required for the export of capsular polysaccharides through the periplasm and across the outer membrane of Gram-negative bacteria.
  2. Structural basis for substrate recognition by ABC transporters involved in the export of bacterial cell-surface polysaccharides.
  3. Structure and function studies of prokaryotic glycosyltransferase enzymes.
  4. Mechanisms that couple glycan biosynthesis and chain extension to transport pathways.

Selected Publications

Nickerson, N.N., I.L. Mainprize, L. Hampton, M.L. Jones, J.H. Naismith and C. Whitfield. 2014. Trapped translocation intermediates establish the route for export of capsular polysaccharides across Escherichia coli outer membranes. Proceedings of the National Academy of Sciences USA 111: in press.

King, J.D., S. Berry, B.R. Clarke, R.J. Morris and C. Whitfield. 2014. Lipopolysaccharide O antigen size distribution is determined by a chain extension complex of variable stoichiometry in Escherichia coli O9a. Proceedings of the National Academy of Sciences USA 111: 6407-6412.

Willis, L.M., and C. Whitfield. 2013. KpsC and KpsS are retaining 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferases involved in synthesis of bacterial capsules. Proceedings of the National Academy of Sciences USA 110: 20753-20758.  

Mainprize, I.L., J.D. Bean, C. Bouwman, M.S. Kimber, and C. Whitfield. 2013. The UDP-glucose dehydrogenase of E. coli K-12 displays substrate inhibition by NAD that is relieved by nucleotide triphosphates. Journal of Biological Chemistry 288: 23064-23074.

Willis, L.M., J. Stupak, M.R. Richards, T.L. Lowary, J. Li, and C. Whitfield. 2013. Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens. Proceedings of the National Academy of Sciences USA 110: 7868-7873.

Bushell, S.R., I.L. Mainprize, M.A. Wear, H. Lou, C. Whitfield, and J.H. Naismith. 2013. Wzi is an outer membrane lectin that underpins group 1 capsule assembly in Escherichia coli. Structure 21: 844-853.

Hageleuken, G., H. Huang, B.R. Clarke, T. Lebl, C. Whifield and J. Naismith. 2012. Structure of WbdD; a bifunctional kinase and methyltransferase that regulates the chain length of the O antigen in Escherichia coli O9a. Molecular Microbiology. 86: 730-742.

Greenfield, L.K, M.R. Richards, E. Vinogradov, W.W. Wakarchuk, T.L. Lowary, C. Whitfield. 2012. Domain organization of the polymerizing mannosyltransferases involved in the synthesis of the Escherichia coli O8 and O9a lipopolysaccharide O antigens. Journal of Biological Chemistry 287: 38135-38149.

Greenfield, L.K., M.R. Richards, J. Li, W.W. Wakarchuk, T.L. Lowary, and C. Whitfield. 2012. Biosynthesis of the polymannose lipopolysaccharide O antigens from Escherichia coli serotypes O8 and O9a requires a unique combination of single- and multi-active site mannosyltransferases. Journal of Biological Chemistry 287: 35078-35091.

Clarke, B.R., M.R. Richards, L.K. Greenfield, D. Hou, T.L. Lowary, and C. Whitfield. 2011. In vitro reconstruction of the chain termination reaction in biosynthesis of the Escherichia coli O9a O-polysaccharide; the chain-length regulator, WbdD, catalyzes the addition of methyl phosphate to the non-reducing terminus of the growing glycan. Journal of Biological Chemistry 286: 41391-41401.

Larue, K., R.C. Ford, L.M. Willis and C. Whitfield. 2011. Functional and structural characterization of polysaccharide co-polymerase proteins required for polymer export in ATP-binding cassette transporter-dependent capsule biosynthesis pathways. Journal of Biological Chemistry 286: 16658-16668.

Cuthbertson, L., M. Kimber and C. Whitfield. 2007. Substrate binding by a bacterial ABC-transporter involved in polysaccharide export. Proceedings of the National Academy of Sciences USA 104: 19529-19534.

Collins, R.F., K. Beis, C. Dong, C. Botting, C. McDonnell, C., R.C. Ford, B.R. Clarke, C. Whitfield, and J.H. Naismith. 2007. The 3-D structure of a novel periplasm-spanning platform required for assembly of group 1 capsular polysaccharides in Escherichia coli. Proceedings of the National Academy of Sciences USA 104: 2390-2395.

Wacker, M., M.F. Feldman, N. Callewaert, B.R. Clarke, N.L. Pohl, M. Hernandez, E.D. Vines, M.A. Valvano, C. Whitfield, and M. Aebi. 2006. Substrate specificity of bacterial  oligosaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems. Proceedings of the National Academy of Sciences USA. 103: 7088-7093.

Dong, C., K. Beis, J. Nesper, A.L. Brunkan, B.R. Clarke, C. Whitfield, and J.H. Naismith. 2006. Wza, the translocon for E. coli capsular polysaccharides defines a new class of membrane protein. Nature 444: 226-229.

Teaching

MICR*4520 Microbial Cell Biology

Lab Members

Graduate Students

Brittany Hunt (MSc)
Elizabeth Kell (MSc)
Sean Liston (PhD)
Megan Massey (MSc)

Postdocs and Research Associates

Brad Clarke
Colin Cooper
Iain Mainprize
Nicholas Nickerson

Lab tech

Catrien Bouwman

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