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David Byers

PhD (Alberta)


Professor (Biochemistry)

Professor (Pediatrics/ARC)
Department member since 1985

Tupper 9-R
902-494-1666
david.byers@dal.ca

Research:

Protein Structure and Function


Research Areas

My laboratory is not currently accepting new students or postdoctoral fellows

My research uses protein chemistry, proteomics, enzymology, and molecular biology to study key proteins involved in lipid metabolism, membrane function, and signal transduction. Current emphasis is on the structure and function of acyl carrier protein (ACP) and its role in bacterial growth and pathogenesis.

ACP is a small (70-80 amino acid) multifunctional fatty acid carrier that is essential for the synthesis of bacterial fatty acids, phospholipids, lipopolysaccharide (LPS), polyketides, and acylated homoserine lactones involved in quorum sensing. Specific interests include: (i) enzymatic and biophysical approaches (circular dichroism, fluorescence, electrophoresis and NMR) to define the molecular details of how ACP interacts with and presents acyl groups to its partner enzymes, (ii) proteomic characterization of ACP and its binding partners at the Faculty of Medicine's proteomics facility, and (iii) de novo design and screening strategies for development of antibacterial drugs targeted at lipid metabolism. Knowledge of how ACP interacts with different enzymes will allow manipulation of fatty acid composition and design of compounds to specifically block ACP-dependent microbial processes.

Publications

  1. Reid, L., MacLeod, A., Byers, D., Delva, D., Fedak, T., Mann, K., Marrie, T., Merritt, B., and Simpson, C., (2012) Deliberative curriculum inquiry for integration in an MD curriculum: Dalhousie University’s curriculum renewal process Medical Teacher 34:e785-e793
  2. Volkmann, G., Murphy, P.W., Rowland, E.E., Cronan, J.E., Jr., Byers, D.M., (2011) Probing protein dynamics in vivo using backbone cyclization: bacterial acyl carrier protein as a case study. Methods in Protein Chemistry” (H. Tschesche, ed.) DeGruyter Publishing, Berlin:271-294
  3. Volkmann, G., Murphy, P.W., Rowland, E.E., Cronan, J.E., Jr., Liu, X.Q., Blouin, C., and Byers, D.M., (2010) Intein-mediated cyclization of bacterial acyl carrier protein stabilizes its folded conformation but does not abolish function. J. Biol. Chem. 285:8605-8614 [PubMed]
  4. Chan, D.I., Chu, B.C., Lau, C.K., Hunter, H.N., Byers, D.M., and Vogel H.J., (2010) NMR solution structure and biophysical characterization of Vibrio harveyi acyl carrier protein A75H: effects of divalent metal ions J. Biol. Chem. 285:30558-30566 [PubMed]
  5. Chappell, D.S., Patel, N.A., Jiang, K., Watson, J.E., Li, P., Byers, D.M., and Cooper, D.R., (2009) Functional involvement of protein kinase C-betaII and its substrate, MARCKS, in insulin-stimulated glucose transport in L6 rat skeletal muscle cells. Diabetologia 52:901-911 [PubMed]
  6. Gong, H., Murphy, P.W., Langille, G.M., Minielly, S., Murphy, A., McMaster, C.R., and Byers, D. M., (2008) Tryptophan fluorescence reveals induced folding of Vibrio harveyi acyl carrier protein upon interaction with partner enzymes. BBA Proteins and Proteomics 1784:1835-1843 [PubMed]
  7. Gong, H., Murphy, A., McMaster, C.R. and Byers, D.M. , (2007) Neutralization of acidic residues in helix II stabilizes the folded conformation of acyl carrier protein and variably alters its function with different enzymes. J. Biol. Chem. 282:4494-4503 [PubMed]
  8. Zheng, Q., Song, J., Doncaster, K., Rowland, E., and Byers, D., (2007) Qualitative and quantitative evaluation of protein extraction protocols for apple and strawberry fruit suitable for two-dimensional electrophoresis and mass spectrometry analysis. J. Agric. Food Chem, 55:1663-1673 [PubMed]
  9. Al-Hertani, W., Yan, S.R., Byers, D.M. and Bortolussi, R., (2007) Human newborn polymorphonuclear neutrophils exhibit decreased levels of MyD88 and attenuated p38 phosphorylation in response to lipopolysaccharide. Clin. Invest. Med. 30:E44-E53
  10. Murphy, P.W., Rowland, E.E., and Byers, D.M., (2007) Electrospray ionization mass spectra of acyl carrier protein are insensitive to its solution phase conformation. J. Amer. Soc. Mass Spectrom. 18(8):1525-1532 [PubMed]
  11. Morash, S.M., Douglas, D., Cook, H.W., McMaster, C.R., and Byers, D.M., (2005) Expression of MARCKS Effector Domain Mutants Alters Phospholipase D Activity and Cytoskeletal Morphology of SK-N-MC Neuroblastoma Cells Neurochem. Res. 11:1353-1364 [PubMed]
  12. Yan, S.R., Qing, G., Byers, D.M., Stadnyk, A.W., Al-Hertani, W., and Bortolussi, R., (2004) Role of MyD88 in diminished TNF-a production by newborn mononuclear cells in response to lipopolysaccharide. Infect. Immun. 72:1223-1229 [PubMed]
  13. Sundaram, M., Cook, H.W., and Byers, D.M., (2004) The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components. Biochem. Cell Biol. 82:191-200 [PubMed]
  14. Yan, S. R., Byers, D. M., and Bortolussi, R., (2004) Role of protein tyrosine kinase p53/p56lyn in diminished lipopolysaccharide priming of fMLP-induced superoxide production in human newborn neutrophils Infect. Immun. 72:6455-6462 [PubMed]
  15. Gong, H. and Byers, D.M., (2003) Glutamate-41 of Vibrio harveyi acyl carrier protein is essential for fatty acid synthase but not acyl-ACP synthetase activity. Biochem. Biophys. Res. Commun. 302:35-40 [PubMed]
  16. Yan, S.R., Al-Hertani, W., Byers, D., and Bortolussi, R., (2002) Lipopolysaccharide-binding protein- and CD14-dependent activation of mitogen-activated protein kinase p38 by lipopolysaccharide in human neutrophils is associated with priming of respiratory burst. Infection and Immunity 70:4068-4074 [PubMed]
  17. Keating, M.M., Gong, H., and Byers, D.M., (2002) Identification of a key residue in the conformational stability of acyl carrier protein. Biochim. Biophys. Acta 1601:208-214 [PubMed]
  18. Byers D. M. and Shen, Z., (2002) Biochemical evidence against protein-mediated uptake of myristic acid in the bioluminescent marine bacterium Vibrio harveyi. Can. J. Microbiol. 48:933-939 [PubMed]
  19. Bonner, S., Yan, S.R., Byers, D.M., and Bortolussi, R., (2001) Activation of ERK 1 and 2 of the MAP kinase family by lipopolysaccharide requires plasma in neutrophils from adult and newborns. Infection and Immunity 69:3143-3149 [PubMed]
  20. Flaman, A.S., Chen, J.M., Van Iderstine, S.C., and Byers, D.M., (2001) Site-directed mutagenesis of acyl carrier protein reveals amino acid residues important for ACP structure and acyl-ACP synthetase activity. J. Biol. Chem. 276:35934-35939 [PubMed]