Research in my laboratory involves human blood proteins involved in coagulation and in iron homeostasis. Using molecular genetic techniques, we have expressed recombinant forms of many human proteins in bacteria, yeast and mammalian cells. By using in vitro mutagenesis, we have studied structural-functional relationships in many of these proteins. For example, we have expressed recombinant human prothrombin as well as sub-fragments and mutants of this protein.
In collaboration with Dr. William Velander ( University of Nebraska – Lincoln ), we are currently expressing recombinant proteins for inclusion in a hemostatic bandage.
In collaboration with local hematologists including Drs. Carter, Wadsworth , Wu, Vickars and Zypchen, we are studying the molecular basis of inherited disorders of hemostasis. Current studies include patients with bleeding problems (such as hemophilia), individuals who clot too much (thrombophilia), individuals with hemoglobinopathies and others. Determination of the molecular basis of such disorders often reveals functional aspects of the human proteins.
My laboratory also studies proteins involved in iron absorption and transport including transferrin, hephaestin and ferroportin. We have recently extended these studies to include yeast iron homeostasis. In a long-term collaboration with Dr. Ann Mason ( University of Vermont ), we are studying the transferrin-transferrin receptor interaction.
Lastly, in collaboration with Dr. Scott Dunbar (Mining Engineering, UBC), we have isolated filamentous bacteriophage that recognize minerals such as chalcopyrite and sphalerite that are of commercial importance in BC. We propose to determine the molecular basis of the phage-mineral recognition and utilize the phage in the final stages of mineral processing.
Curtis SB, Dunbar WS, Macgillivray RT. Bacteriophage-induced aggregation of oil sands tailings. Biotechnol Bioeng. 2012 Oct 10.
Vanden Hoek AL, Talbot K, Carter IS, Vickars L, Carter CJ, Jackson SC, Macgillivray RT, Pryzdial EL. Coagulation factor X Arg386 specifically affects activation by the intrinsic pathway: a novel patient mutation. J Thromb Haemost. 2012 Dec;10(12):2613-5.
Vashchenko G, Macgillivray RT. Functional role of the putative iron ligands in the ferroxidase activity of recombinant human hephaestin. J Biol Inorg Chem. 2012 Dec;17(8):1187-95.
Grieco SH, Wong AY, Dunbar WS, MacGillivray RT, Curtis SB. Optimization of fermentation parameters in phage production using response surface methodology. J Ind Microbiol Biotechnol. 2012 Oct;39(10):1515-22.
Steere AN, Chasteen ND, Miller BF, Smith VC, Macgillivray RT, Mason AB. Structure-based mutagenesis reveals critical residues in the transferrin receptor participating in the mechanism of pH-induced iron release from human serum transferrin. Biochemistry. 2012 Feb 22. [Epub ahead of print]
Steere AN, Miller BF, Roberts SE, Byrne SL, Chasteen ND, Smith VC, Macgillivray RT, Mason AB. Ionic residues of human serum transferrin affect binding to the transferrin receptor and iron release. Biochemistry. 2012 Jan 17;51(2):686-94.
Vashchenko G, Bleackley MR, Griffiths TA, MacGillivray RT. Oxidation of organic and biogenic amines by recombinant human hephaestin expressed in Pichia pastoris. Arch Biochem Biophys. 2011 Oct;514(1-2):50-6.
Bleackley MR, Macgillivray RT. Transition metal homeostasis: from yeast to human disease. Biometals. 2011 Oct;24(5):785-809.
Curtis SB, Macgillivray RT, Dunbar WS. Effects of bacteriophage on the surface properties of chalcopyrite (CuFeS(2) ), and phage-induced flocculation of chalcopyrite, glacial till and oil sands tailings. Biotechnol Bioeng. 2011 Jul;108(7):1579-90.
Bleackley MR, Young BP, Loewen CJ, Macgillivray RT. High density array screening to identify the genetic requirements for transition metal tolerance in Saccharomyces cerevisiae. Metallomics. 2011 Feb 1;3(2):195-205.
Carter, I.S.R., Vanden Hoek, A.L., Pryzdial, E.L.G. and MacGillivray, R.T.A. Thrombin A-chain: activation remnant or allosteric effector? Thrombosis in press (2011)
Steere, A.N., Byrne, S.L., Chasteen, N.D., Smith, V.C., MacGillivray, R.T.A. & Mason, A.B. Evidence that His349 acts as a pH-inducible switch to accelerate receptor- mediated iron release from the C-lobe of human transferrin. J. Biol. Inorg. Chem. 15, 1341-1352 (2010)
Talbot, K., Song, J., Hewitt, J., Serrano, K., Ho, M., Carter, C.J., MacGillivray, R.T.A. & Pryzdial, E.L.G. A novel compensating mechanism for homozygous coagulation factor V deficiency suggested by enhanced activated partial thromboplastin time after reconstitution with normal factor V. Br. J. Haematol. 151, 198-200 (2010)
Steere, A.N., Roberts, S.E., Byrne, S.L., Chasteen, D., Bobst, C.E., Katlashov, I.A., Smith, V.C., MacGillivray, R.T.A. & Mason, A.B. Novel strategy to produce homogeneous human transferrin C-lobe by introduction of a TEV cleavage site into the bridge between the lobes. Protein Expr. Purif. . 72, 32-41 (2010)
Hudson, D.M., Curtis, S.B., Smith, V.C., Griffiths, T.A.M., Wong, A.Y.K., Scudamore, C.H., Buchan, A.M.J. & MacGillivray, R.T.A. Human hephaestin expression is not limited to enterocytes of the GI tract but is also found in the antrum, the enteric nervous system and pancreatic beta-cells. Am. J. Physiol. Gastrointest. Liver Physiol. 298, G425-432 (2009)
Mason, A.B., Byrne, S.L., Everse, S.J., Roberts, S.E., Chasteen, N.D., Smith, V.C., MacGillivray, R.T.A., Kandemir, B. & Bou-Abdallah, F. A loop in the N-lobe of human serum transferrin is critical to binding to the transferrin receptor as revealed by mutagenesis, isothermal titration calorimetry and epitope mapping. J. Molec. Recog. 22, 521-529 (2009)
Song, J., Talbot, K., Hewitt, J., MacGillivray, R.T.A. & Pryzdial, E.L.G. Differential contribution of Glu96, Asp102 and Asp111 to coagulation factor Va subunit stability. Biochem. J. 422, 257-264 (2009)
James, N.G., Byrne, S.L., Steere, A.N., Smith, V.C., MacGillivray, R.T.A. & Mason, A.B. Inequivalent Contribution of the five tryptophan residues in the C-lobe of human serum transferrin to the fluorescence increase when iron is released Biochemistry 48, 2858-2867 (2009)
Grieco, S-H.H., Lee, S., Dunbar, W.S., MacGillivray, R.T.A. & Curtis, S.B. Maximizing filamentous phage yield during computer-controlled fermentation. Bioprocess. Biosys. Eng. 32, 773-779 (2009)
Mason, A.B., Halbrooks, P.J., James, N.G., Byrne, S.L., Grady, J.K., Chasteen, N.D., Bobst , C.E., K altashov , I.A., Smith, V.C., MacGillivray, R.T.A., & Everse, S.J. Structural and functional consequences of the substitution of glycine 65 by arginine in the N-lobe of human transferrin. Biochemistry 48, 1945-1953 (2009)
Au, N.H.C., Wong, A.Y.K., Vickars, L.. MacGillivray, R.T.A. & Wadsworth, L.D. Two new examples of Hemoglobin St. Etienne / Istanbul in association with venous thrombosis. Hemoglobin 33, 95-100 (2009)
Bleackley, M.R., Wong, A.Y.K., Hudson, D.M., Wu, C.H-Y. and MacGillivray, R.T.A. Blood iron homeostasis: newly-discovered proteins and iron imbalance. Transfusion Med. Rev. 23, 103-123 (2009)
Yoon, D.J., Chu, D.S.H., Ng, C.W., Pham E.A., Mason, A.B., Hudson, D.M., Smith, V.C., MacGillivray, R.T.A. & Kamei, D.T. Genetically engineering transferrin to improve its in vitro ability to deliver cytotoxins. J. Control. Release 133, 178-184 (2009)
Curtis, S.B., Hewitt, J., MacGillivray, R.T.A. & Dunbar, W.S. Biomining with bacteriophage: Selectivity of displayed peptides for naturally occurring sphalerite and chalcopyrite. Biotechnol. Bioeng. 102, 644-650 (2009)