Natalie Strynadka

Contact InformationNatalie Strynadka
Life Sciences Centre
#4362 – 2350 Health Sciences Mall
Vancouver, BC, Canada V6T 1Z3
Tel: 1-604-822-0789
Fax: 1-604-822-7729
Email: natalie@byron.biochem.ubc.ca

Current Positions

  • Professor, Biochemistry and Molecular Biology, Medicine.
  • Associate Member, Michael Smith Laboratories.
  • Howard Hughes Senior International Research Scholar.

Research Interests

Resistance to standard antibiotic therapies is a growing health concern around the globe. Certain infections that are essentially untreatable have been identified in both hospital and community settings. The increasing frequency of drug resistance has been attributed to a combination of antibiotic over-prescription and societal and technologic changes that affect the transmission of drug-resistant organisms.

The ultimate goal of the research in our laboratory is the structure-based design of novel, therapeutically useful antibiotics and inhibitors of antibiotic-resistance mechanisms. To achieve this goal we use a combination of x-ray crystallography, molecular modelling, molecular docking and molecular biology in collaboration with medicinal chemistry to engineer drugs that specifically interact with and disable critical bacterial target proteins.

Selected Publications

  1. Zeytuni N, Flanagan KA, Worrall LJ, Massoni SC, Camp AH, Strynadka NCJ. Structural and biochemical characterization of SpoIIIAF, a component of a sporulation-essential channel in Bacillus subtilis. J Struct Biol. 2018 Oct;204(1):1-8.
  2. Zeytuni N, Flanagan KA, Worrall LJ, Massoni SC, Camp AH, Strynadka NCJ. Structural characterization of SpoIIIAB sporulation-essential protein in Bacillus subtilis. J Struct Biol. 2018 May;202(2):105-112. doi: 10.1016/j.jsb.2017.12.009.
  3. Workman SD, Worrall LJ, Strynadka NCJ.Crystal structure of an intramembranal phosphatase central to bacterial cell-wall peptidoglycan biosynthesis and lipid recycling. Nat Commun. 2018 Mar 20;9(1):1159. doi: 10.1038/s41467-018-03547-8.
  4. Volkers G, Lizak C, Niesser J, Rosell FI, Preidl J, Gnanapragassam VS,Horstkorte R, Rademann J, Strynadka NCJ. Structural Basis for Binding of Fluorescent CMP-Neu5Ac Mimetics to Enzymes of the Human ST8Sia Family. ACS Chem Biol. 2018 Aug 17;13(8):2320-2328.
  5. Majewski DD, Worrall LJ, Strynadka NC. Secretins revealed: structural insights into the giant gated outer membrane portals of bacteria. Curr Opin Struct Biol. 2018 Aug;51:61-72. doi: 10.1016/j.sbi.2018.02.008. Epub 2018 Mar 23.
  6. Hu J, Worrall LJ, Hong C, Vuckovic M, Atkinson CE, Caveney N, Yu Z, Strynadka NCJ. Cryo-EM analysis of the T3S injectisome reveals the structure of the needle and open secretin. Nat Commun. 2018 Sep 21;9(1):3840.
  7. Crowe AM, Workman SD, Watanabe N, Worrall LJ, Strynadka NCJ, Eltis LD. IpdAB, a virulence factor in Mycobacterium tuberculosis, is a cholesterol ring-cleaving hydrolase. Proc Natl Acad Sci USA. 2018 Apr 10;115(15):E3378-E3387.
  8. Caveney NA, Li FK, Strynadka NC. Enzyme structures of the bacteria peptidoglycan and wall teichoic acid biogenesis pathways. Curr Opin Struct Biol. 2018 Dec;53:45-58.
  9. Blaukopf M, Worrall L, Kosma P, Strynadka NCJ, Withers SG. Insights into Heptosyltransferase I Catalysis and Inhibition through the Structure of Its Ternary Complex. Structure. 2018 Oct 2;26(10):1399-1407.e5.
  10. Bergeron JRC, Brockerman JA, Vuckovic M, Deng W, Okon M, Finlay BB, McIntosh LP, Strynadka NCJ. Characterization of the two conformations adopted by the T3 SS inner-membrane protein PrgK. Protein Sci. 2018 Sep;27(9):1680-1691.
  11. Basuino L, Jousselin A, Alexander JAN, Strynadka NCJ, Pinho MG, Chambers HF, Chatterjee SS. PBP4 activity and its overexpression are necessary for PBP4-mediated high-level β-lactam resistance. J Antimicrob Chemother. 2018 May 1;73(5):1177-1180.
  12. Alexander JAN, Chatterjee SS, Hamilton SM, Eltis LD, Chambers HF, Strynadka NCJ. Structural and kinetic analyses of penicillin-binding protein 4 (PBP4)-mediated antibiotic resistance in Staphylococcus aureus. J Biol Chem. 2018 Dec 21;293(51):19854-19865. doi: 10.1074/jbc.RA118.004952. Epub 2018 Oct 26.
  13. King DT, Wasney GA, Nosella M, Fong A, Strynadka NC. Structural Insights into Inhibition of Escherichia coli Penicillin-binding Protein 1B. J Biol Chem. 2017 Jan 20;292(3):979-993. doi: 10.1074/jbc.M116.718403. Epub 2016 Nov 29.
  14. Baradaran-Heravi A, Niesser J, Balgi AD, Choi K, Zimmerman C, South AP, Anderson HJ, Strynadka NC, Bally MB, Roberge M. Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity. Proc Natl Acad Sci USA. 2017 Mar 28;114(13):3479-3484.
  15. Worrall LJ, Hong C, Vuckovic M, Deng W, Bergeron JR, Majewski DD, Huang RK, Spreter T, Finlay BB, Yu Z, Strynadka NC. Near-atomic-resolution cryo-EM analysis of the Salmonella T3S injectisome basal body. Nature. 2016 Dec 14.
  16. Sobhanifar S, Worrall LJ, King DT, Wasney GA, Baumann L, Gale RT, Nosella M, Brown ED, Withers SG, Strynadka NC. Structure and Mechanism of Staphylococcus aureus TarS, the Wall Teichoic Acid β-glycosyltransferase Involved in Methicillin Resistance. PLoS Pathog. 2016 Dec 14;12(12):e1006067.
  17. Myers CL, Li FK, Koo BM, El-Halfawy OM, French S, Gross CA, Strynadka NC, Brown ED. Identification of Two Phosphate Starvation-induced Wall Teichoic Acid Hydrolases Provides First Insights into the Degradative Pathway of a Key Bacterial Cell Wall Component. J Biol Chem. 2016 Dec 9;291(50):26066-26082. Epub 2016 Oct 25.
  18. King DT, Wasney GA, Nosella M, Fong A, Strynadka NC. Structural Insights into Inhibition of Escherichia coli Penicillin-binding Protein 1B. J Biol Chem. 2017 Jan 20;292(3):979-993. doi: 10.1074/jbc.M116.718403. Epub 2016 Nov 29.
  19. King DT, Sobhanifar S, Strynadka NC. One ring to rule them all: Current trends in combating bacterial resistance to the β-lactams. Protein Sci. 2016 Apr;25(4):787-803.
  20. King AM, King DT, French S, Brouillette E, Asli A, Alexander JA, Vuckovic M, Maiti SN, Parr TR Jr, Brown ED, Malouin F, Strynadka NC, Wright GD. Structural and Kinetic Characterization of Diazabicyclooctanes as Dual Inhibitors of Both Serine-β-Lactamases and Penicillin-Binding Proteins. ACS Chem Biol. 2016 Apr 15;11(4):864-8. doi: 10.1021/acschembio.5b00944.
  21. Bergeron, J.R., L. Fernández, G.A. Wasney, M. Vuckovic, F. Reffuveille, R.E.W. Hancock, and N.C. Strynadka. 2016. The structure of a type 3 secretion system ruler protein suggests a molecular mechanism for needle length sensing. J Biol Chem. 291:1676-1691.
  22. Bergeron JR, Fernández L, Wasney GA, Vuckovic M, Reffuveille F, Hancock RE, Strynadka NC. The Structure of a Type 3 Secretion System (T3SS) Ruler Protein Suggests a Molecular Mechanism for Needle Length Sensing. J Biol Chem. 2016 Jan 22;291(4):1676-91. doi: 10.1074/jbc.M115.684423. Epub 2015 Nov 20.
  23. Volkers G, Worrall LJ, Kwan D, Yu CC, Baumann L, Lameignere E, SCOTT NE, Foster LJ, Withers SG, Strynadka NCJ. (2015). Structure of human ST8SiaIII sialyltransferase provides insight into cell surface polysialylation. Nature Structural & Molecular Biology. 22(8): 627-635.
  24. Tsai CL, Burkinshaw BJ, Strynadka NC, Tainer JA. The Salmonella type III secretion system virulence effector forms a new hexameric chaperone assembly for export of effector/chaperone complexes. J Bacteriol. 2015 Feb 15;197(4):672-5.
  25. Solomonson M, Setiaputra D, Makepeace KAT, Lameignere E, Petrotchenko EV, Conrady DG, Bergeron JR, Vuckovic M, DiMaio F, Borchers CH, Yip CK, Strynadka NCJ. Structure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism. Structure. 2015 Mar 3;23(3):571-583.
  26. Sobhanifar S, Worrall LJ, Gruninger RJ, Wasney GA, Blaukopf M, Baumann L, Lameignere E, Solomonson M, Brown ED, Withers SG, Strynadka NC. Structure and mechanism of Staphylococcus aureus TarM, the wall teichoic acid α-glycosyltransferase. Proc Natl Acad Sci USA. 2015 Feb 10;112(6):E576-85.
  27. King DT, King AM, Lal SM, Wright GD, Strynadka NC. Molecular Mechanism of Avibactam-Mediated β-Lactamase Inhibition. ACS Infect Dis. 2015 Apr 10;1(4):175-84. doi: 10.1021/acsinfecdis.5b00007. Epub 2015 Feb 11.
  28. Ghavami A, Labbé G, Brem J, Goodfellow VJ, Marrone L, Tanner CA, King DT, Lam M, Strynadka NC, Pillai DR, Siemann S, Spencer J, Schofield CJ, Dmitrienko GI. Assay for drug discovery: Synthesis and testing of nitrocefin analogues for use as β-lactamase substrates. Anal Biochem. 2015 Oct 1;486:75-7.
  29. Farha MA, Czarny TL, Myers CL, Worrall LJ, French S, Conrady DG, Wang Y, Oldfield E, Strynadka NC, Brown ED. Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase. Proc Natl Acad Sci USA. 2015 Sep 1;112(35):11048-53.
  30. Burkinshaw BJ, Souza SA, Strynadka NC. Structural analysis of SepL, an enteropathogenic Escherichia coli type III secretion-system gatekeeper protein. Acta Crystallogr F Struct Biol Commun. 2015 Oct;71(Pt 10):1300-8.

Education

  • Ph.D. University of Alberta, 1990.
  • B.Sc. University of Alberta, 1984.