Associate Professor Tom Brittain

Molecular, Cellular & Developmental Biology

Phone: 09-3737599 x88246
Rm 402B
Email: t.brittain@auckland.ac.nz

Metalloprotein Structure & Function Laboratory

General areas of interest:

Physical Biochemistry: in particular the study of the structure and mode of action of metalloproteins (primarily heme proteins). Functional studies range from fundamental theoretical and physico-chemical characterisation to investigations of actions in vivo and in cell culture.

Current main interest:

The role of neuroglobin in the protection of neurons from apoptotic cell death.

The protein Neuroglobin has been expressed in E. coli. and the protein ligand binding kinetics investigated [134]. A new reactivity of neuroglobin towards H2S has been investigated [141]. The kinetics of inter-molecular electron transfer reactions have been investigated in collaboration with Prof. A. Fago (Aarhus University Denmark). Ferric cytochrome c has been shown to be an extremely active redox partner for ferrous neuroglobin [135]. Based on these findings we have performed structural studies on models of complexes with cytochrome c.

The calculated structure of the neuroglobin-cytochrome c complex.

Surface Plasmon Resonance and N.M.R. investigations of complex formation between cytochrome c and neuroglobin in solution have identified complex formation and have allowed us to determine binding constants and thermodynamic characteristics of the complex formation reaction [147]. Our experimental findings have allowed us to postulate a novel role for neuroglobin in the modulation of apoptosis in neurons and retinal cells [143].

In a major collaborative effort with Prof. S. Raychauduri (University of California, Davis) we have established a systems level numerical model of apoptosis and used this to predict the actions of neuroglobin within the cell. Experimental findings have fully verified the predictions of this model [149-151].

These findings lead us to suggest that neuroglobin may well perform an integrating role in the control of apoptosis:

Recent Publications

[154] Skommer, J., Das, S.C., Nair, A., T Brittain, Raychaudhuri, S (2011). Non-linear regulation of commitment to apoptosis by simultaneous inhibition of Bcl-2 and XIAP in leukemia and lymphoma cells. Apoptosis 16, 619-626.

[153] *T Brittain, Skommer. J, Henty. K, Birch . N. and Raychaudhuri, S (2010). A role for human neuroglobin in apoptosis. IUBMB Life 62, 875-885.

[152] Chien, V., Aitken, J.F., Zhang, S., Buchanan, C., Hickey, A., T Brittain, Cooper, G.J.S. and Loomes, K.M (2010). The chaperone proteins HSP70, HSP40/DnaJ and GRP78/BiP can suppress misfolding and formation of β-sheet-containing aggregates by Human Amylin. Biochem. J. 432, 113-121.

[151] Skommer, J., *T Brittain and Raychaudhuri, S (2010). Bcl-2 inhibits apoptosis by modulating intrinsic cell-to-cell variations in the mitochondrial pathway of cell death. Apoptosis15, 1223-1233.

[150] *T Brittain, Skommer, J., Raychaudhuri, S. and Birch, N (2010). An anti-apoptotic neuroprotective role for neuroglobin. Int. J. Mol. Sci., 11, 2306-2321.

[149] Raychaudhuri, S., Skommer, J., Henty, K., Birch, N., and *T Brittain (2010). Neuroglobin protects nerve cells from apoptosis by inhibiting the intrinsic pathway of cell death. Apoptosis 15, 401- 411.

[148] Rasmussen. J.R., Wells. R.M.G., Henty. K., Clark. T. D., and *T Brittain (2009). Characterization of the hemoglobins of the Australian lungfish Neoceratodus forsteri (Krefft). Comp. Biochem. Physiol. 152, 162-167.

[147] Bonding, S.H. K. Henty, A. Dingley and *T Brittain (2008). The binding of cytochrome c to neuroglobin: a docking and Surface Plasmon Resonance study. Int. J. Biol. Macromol. 43, 295-299.

T Brittain, P D W Boyd, V Fulop and A Echalier. (2008). The mechanism of action of di-heme peroxidases: a theoretical study . (in press) Inorg Biochem. Res. Prog. Hughes. J.G and Robinson A.J. Eds., Nova Science, N.Y., U.S.A.

T Brittain. (2008). Intra-molecular electron transfer in proteins. Protein and Peptide Letters. 15, 556-561.

S Unzai, S Y Park, K Nagai, T Brittain and J R H Tame. (2008). Mutagenic studies on the origins of the Root Effect." in Dioxygen binding and sensing proteins. Protein Reviews Vol. 9. p 67-78. M. Bolognesi, G. di Prisco, C. Verde (Eds) Springer Verlag .

A Fago, A J Mathews and T Brittain. (2008). A role for neuroglobin: resetting the trigger level for apoptosis in neuronal and retinal cells. IUBMB. Life. 60, 398- 401.

T Brittain, Y Yosaatmadja and K Henty. (2008). The interaction of human neuroglobin with hydrogen sulphide . IUBMB Life. 60, 135-138.

A Echalier, T Brittain, J Wright, S Boycheva, G B Mortuza, V Fulop, N J Watmough. (2008). Redox linked structural changes associated with the formation of a catalytically competent form of the diheme cytochrom c peroxidase from Pseudomonas aeruginosa. Biochemistry 47, 1947-1956.

T Brittain. (2008). Extreme pH sensitivity in the binding of oxygen to some fish hemoglobins. The smallest biomolecules: Diatomics and their interactions with heme- proteins. p 219-235. (Ed. A.Ghosh), Elsevier.

K Henty, R M G Wells and T Brittain. (2007). Characterisation of the hemoglobins of the adult brushtailed possum, Trichosurus vulpecula (Kerr) reveals non- genetic functional heterogeneity . Comp. Biochem. Physiol. 148, 498-503.

Y Lee, S Svetlana Boycheva, T Brittain and P D W Boyd. (2007). Evidence for a possible charge hopping mechanism for intra-molecular electron transfer in the cytochrome c peroxidase of Pseudomonas aeruginosa . Chem Bio Chem, 8, 1440- 1446.

H Hsiao, S Boycheva, N J Watmough and T Brittain. (2007). The role of a heme linked protein loop in the activation of cytochrome c peroxidase of Pseudomonas aeruginosa: mutagenesis studies . Journal of InorganicBiochemistry 101, 1133-1139.

A Fago, A J Mathews, L Moens, S Dewilde and T Brittain. (2006). Reactivity of neuroglobin with the potential redox protein partners cytochrome b5 and cytochrome c . FEBS. Letts. 580, 4884- 4888.

A Fago, A J Mathews, S Dewilde, L Moens and T Brittain. (2006). The reactions of neuroglobin with CO:evidence for two forms of the ferrous protein . J. Inorg. Biochem. 100, 1339-1343.

R M G Wells, J Baldwin, R S Seymour, K Christian and T Brittain (2005). Red blood cell function and haematology in two tropical freshwater fishes from Australia . Comp. Biochem. Physiol 141, 87-93.

T Rasmussen, T Brittain, B C Berks, N J Watmough and A J Thomson. (2005). Formation of a cytochrome c- Nitrous oxide reductase complex is obligatory for N2O reduction by Paracoccus Pantotrophus. Dalton Transactions 21, 3501-3506.

T Brittain. (2005). The Root Effect Hemoglobins. J. Inorg. Biochem. 99, 120-130..

<< Our People < Dr Svetlana Boycheva | Anna Brooks >