(departmental, undergrad and grad program correspondence)
Office: SCIE 4477
Lab: SCIE 4202
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.
B.Sc. University of Newcastle-upon-Tyne
Ph.D. University of Edinburgh
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:
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.
Structural basis for substrate recognition by ABC transporters involved in the export of bacterial cell-surface polysaccharides.
Biosynthesis of the lipopolysaccharide core oligosaccharides and their role in outer membrane stability.
Structure and function studies of prokaryotic glycosyltransferase enzymes.
Regulation of bacterial polysaccharide polymerases.
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.
Tran, A.X., C. Dong and C. Whitfield. 2010. Structure and functional analysis of LptC, a conserved membrane protein involved in the lipopolysaccharide export pathway in Escherichia coli. Journal of Biological Chemistry 285; 33529-33539.
Cuthbertson, L., V. Kos and C. Whitfield. 2010. ABC transporters involved in the export of cell-surface glycoconjugates. Microbiology and Molecular Biology Reviews. 74: 341-362.
Kos, V., and C. Whitfield. 2010. A membrane-located glycosyltransferase complex required for biosynthesis of the D-galactan I polysaccharide O antigen in Klebsiella pneumoniae. Journal of Biological Chemistry 285: 19668-19687.
Clarke, B.R., L.K. Geenfield, C. Bouwman, and C. Whitfield. 2009. Coordination of polymerization, chain termination, and export in assembly of the Escherichia coli lipopolysaccharide O9a antigen in an ABC transporter-dependent pathway. Journal of Biological Chemistry 284: 30662-30772.
Hageleuken, G., H. Huang, I.L. Mainprize, C. Whitfield, and J.H. Naismith. 2009. Crystal structures of Wzb of Escherichia coli and CpsB of Streptococcus pneumoniae, representatives of two different families of tyrosine phosphatases that regulate capsule assembly. Journal of Molecular Biology. 392: 678-688.
Cuthbertson, L., I. Mainprize, J.H. Naismith, and C. Whitfield. 2009. Export of extracellular polysaccharides in Gram-negative bacteria; the pivotal roles of OPX and PCP protein families. Microbiology and Molecular Biology Reviews. 73: 155-177.
Larue, K., M. Kimber, R. Ford and C. Whitfield. 2009. Biochemical and structural analysis of bacterial O antigen chain length regulator proteins reveals a conserved quaternary structure. Journal of Biological Chemistry. 283: 7395-7403.
Kos, V., L. Cuthbertson, and C. Whitfield. 2009. The Klebsiella pneumoniae O2a antigen defines a second mechanism for O antigen ABC transporters. Journal of Biological Chemistry. 283: 284: 2947-2956.
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.
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.
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.
MICR*3270 Microbial Cell Biology
Laura Greenfield (Ph.D.)
Lisa Willis (Ph.D.)
Brittany Hunt (M.Sc.)