Culvenor Laboratory

Study of the expression, localization, and function of key proteins associated with neurodegeneration in Alzheimer's disease and Synuclein-associated diseases including Parkinson's and Dementia with Lewy bodies.

Location:

Neurodegeneration Laboratory, Centre for Neuroscience

Staff and Students:

Dr Janetta Culvenor - Laboratory Head

Dr Su San Mok - Senior Research Fellow

Nancy Ilaya - PhD student

Sonia George - PhD student

Projects

• Study of nature of and localization of presenilin protein complexes and identification of novel components
• Study of role of nicastrin in brain and muscle protein complexes
• Establishment of cell culture model of intracellular a-synuclein aggregation to examine the process of aggregation and modifiers
• Development of reagents and detection of new gene products associated with Parkinson's disease
• Study of animal models of Parkinson's disease

Techniques

• Development and characterization of antibodies
• SDS polyacrylamide gel electrophoresis and Blue native gel electrophoresis
• Primary cell and cell line tissue culture
• Western blotting of cultured cell extracts, animal tissue, and human brain
• Laser confocal microscopy and immunofluorescence
• Immunocytochemistry
• Transmission electron microscopy and immunogold labelling

Collaborations

Departmental : G. Evin, Q.X. Li, R. Cappai, K. Barnham, C. McLean, F. Ali

University of Melbourne: Ann Turnley, Centre for Neuroscience

External: W.P. Gai, Flinders University (Department of Human Physiology)

M. Ryan, La Trobe University (Department of Biochemistry)

Funding

• NHMRC
• Prana Biotechnology Ltd
• Neurosciences Victoria Ltd
• ANZ Charitable Trusts

Recent Publications

• Evin, G., Canterford, L.D., Hoke, D.E., Sharples, R.A., Culvenor, J.G., and Masters, C.L. (2005) Transition-state analogue gamma-secretase inhibitors stabilize a 900 kDa presenilin/nicastrin complex. Biochem . 44 , (4332-4341)

• Cappai R, Leck SL, Tew DJ, Williamson NA, Smith DP, Galatis D, Sharples RA, Curtain CC, Ali FE, Cherny RA, Culvenor JG , Bottomley SP, Masters CL, Barnham KJ, and Hill AF (2005) Dopamine promotes a-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway. FASEB J, online June 9.
• Culvenor, J.G., Ilaya, N.T., Ryan, M.T., Canterford, L., Hoke, D., Williamson, N.A., McLean, C.A., Masters, C.L., and Evin, G. (2004) Characterization of Presenilin Complex from Mouse and Human Brain using Blue Native Gel Electrophoresis Reveals High Expression in Embryonic Brain and Minimal Change in Complex Mobility with Presenilin Mutations. Eur. J. Biochem. 271 , 375-385.
• Ilaya, NT., Evin, G., Masters, CL., and Culvenor, JG. (2004) Nicastrin expression in mouse peripheral tissues is not co-ordinated with Presenilin and is high in muscle . J. Neurochem. 91, 230-237.
• Smith, M. J., Sharples, R.A., Evin, G., McLean, C.A., Dean, B., Pavey, G., Fantino, E., Cotton, R.G.H., Imaizumi, K., Masters, C.L., Cappai, R., and Culvenor , J.G. (2004) Expression of truncated Presenilin 2 splice variant in Alzheimer's Disease, Bipolar Disorder, and Schizophrenia brain cortex . Molec. Brain Res. 127, 128-135.
• Gai, W.P., Pountney , D.L., Power, J.H.T., Li,Q.-X., Culvenor, J.G., McLean , C.A. , Jensen, P.H., and Blumbergs, P.C. (2003 ) a-Synuclein Fibrils Constitute the Central Core of Oligodendroglial Inclusion Filaments in Multiple System Atrophy. Exp. Neurol . 181 , 68-78.
• Sernee, M.F., Evin G., Culvenor J.G. , Villadangos, J.A., Beyreuther, K., Masters, C.L., and Cappai, R. (2003) Selecting cells with different Alzheimer's disease gamma-secretase activity using FACS. Differential effect on presenilin exon 9 gamma- and epsilon-cleavage. Eur. J. Biochem. 270 , 495-506.
• Beher, D., Fricker, M., Nadin, A., Clarke, E.E., Wrigley, J.D.J., Li, Y.-M., CULVENOR, J.G., Masters, C.L., Harrison , T., and Shearman, M.S. (2003) In Vitro Characterization of the Presenilin-dependent g-secretase Complex Using a Novel Affinity Ligand. Biochem. 42 , 8133-8142.
• Wickham , M.E. , Culvenor, J.G., and Cowman, A.F. (2003) Selective Inhibition of a Two-step Egress of Malaria Parasites from the Host Erythrocyte. J. Biol. Chem . 278 , 37658-37663.
• Culvenor, J.G., Rietze, R.L., Bartlett, P.F., Masters, C.L., and Li, Q.-X. (2002) Oligodendrocytes from Neural Stem Cells Express alpha-Synuclein: Increased Numbers from Presenilin 1 Deficient Mice. NeuroReport 13, 1305-1308.
• Mok, S.S., Turner, B.J., Beyreuther, K., Masters, C.L., Barrow, C.J., and Small, D.H. (2002) Toxicity of substrate bound amyloid peptides on vascular smooth muscle cells is enhanced by homocysteine. Eur. J. Biochem., 269, 3014-3022.
• Mok, S.S., Clippingdale, A.B., Beyreuther, K., Masters, C.L., Barrow, C.J. and Small D.H. (2000) Abeta peptides and calcium influence the secretion of the amyloid protein precursor from chick sympathetic neurons in culture. J. Neurosci Res. 15, 449-457.
• Culvenor, J.G., Evin, G., Cooney, M.A., Wardan, H., Robyn A. Sharples, Maher, F., Reed, G., Diehlmann, A., Weidemann, A., Beyreuther, K., and Masters, C.L. (2000) Presenilin 2 expression in neuronal cells: Induction during differentiation of embryonic carcinoma cells. Exp. Cell Res. 255, 192-206.
• Culvenor, J.G., McLean, C.A., Cutt, S., Campbell, B.C.V., Maher, F., Jäkälä, P., Hartmann, T., Beyreuther, K., Masters, C.M., and Qiao-Xin Li. (1999) Non-Abeta component of Alzheimer's disease amyloid (NAC) revisited: NAC and alpha-synuclein are not associated with Abeta amyloid. Am. J. Path. 155, 1173-1181
• Culvenor, J.G., Henry, A., Hartmann, T., Evin, G., Galatis, D., Friedhuber, A., Jayasena, U. L. H. R., Underwood, J.R., Beyreuther, K., Masters, C.L. and Cappai, R. (1998) Subcellular localization of the Alzheimer's disease amyloid precursor protein and derived peptides expressed in a recombinant yeast system. Amyloid Int. J. Exp. Clin. Invest. 5, 79-89.