Prof. Vladimir Buchman
Based at the Pathophysiology & Repair Division, School of Biosciences
Neuronal death, axonal and synaptic damage, neurodegeneration, Parkinson’s disease, physiological function of synucleins, ALS/FTLD, FUS, TDP-43, C9ORF72
Research Interests and Facilities
The aim of our studies is to reveal molecular and cellular mechanisms of neuronal differentiation, and to find links between developmental processes and neuronal dysfunction associated with neurodegenerative diseases and ageing.
Available PhD Projects
Studies of function and dysfunction of synucleins.
Alpha-synuclein is involved in neurodegeneration associated with Parkinson’s disease and other synucleinopathies but physiological function(s) of this protein, as well as two other members of the family, beta- and gamma-synuclein, is still not fully understood. We believe that revealing the role of synucleins in developing and mature nervous system will help to identify molecular and cellular events associated with synuclein dysfunction in neurodegenerative diseases.
Molecular and cellular mechanisms of motor neuron damage in amyotrophic lateral sclerosis (ALS).
Recent progress in studies of aetiology and pathogenesis of ALS revealed several new genes and proteins associated with familial and sporadic forms of this disease. To model ALS pathology in vivo we have produced transgenic mice expressing proteins involved in pathogenesis of this disease, including gamma-synuclein and modified forms of FUS. We hope that detailed studies of in vivo as well as cellular models of these proteinopathies will shed light on molecular and cellular mechanisms of dysfunction and ultimately, death of neurons affected in ALS.
Our main tools are animal models - knock-out (including double and, in case of synucleins, even triple knock-outs), transgenic and knock-in mice. Histology, primary cultures, behavioural tests and biochemical methods are used for characterisation of previously generated and new mouse lines.
- V.L.Buchman, J.Adu, L.G.P.Pinon, N.N.Ninkina and A.M.Davies (1998) Persyn, a member of the synuclein family, influences neurofilament network integrity. Nature Neuroscience, 1, 101-103
- A.R.Saha, N.N.Ninkina, D.P.Hanger, B.H.Anderton, A.M.Davies and V.L.Buchman (2000) Induction of neuronal death by alpha-synuclein. European Journal of Neuroscience, 12, 3073-3077
- N.Ninkina, K.Papachroni, D.C.Robertson, O.Schmidt, L.Delaney, F.O’Neil, F.Court, A.Rosenthal, S.M.Fleetwood-Walker, A.M.Davies and V.L.Buchman (2003) Neurons expressing the highest levels of gamma-synuclein are unaffected by targeted inactivation of the gene. Molecular and Cellular Biology, 23, 8233-8245
- K.K.Papachroni, N.Ninkina, A.Papapanagiotou, G.M.Hadjigeorgiou, G.Xiromerisiou, A.Papadimitriou, A.Kalofoutis and V.L.Buchman (2007) Autoantibodies to alpha-synuclein in inherited Parkinson’s disease. Journal of Neurochemistry, 101,749–756
- N.Ninkina, O.Peters, S.Millership, H.Salem, H.van der Putten and V.L.Buchman (2009) g-synucleinopathy - neurodegeneration associated with overexpression of the mouse protein. Human Molecular Genetics, 18, 1779-1794
- A.Al-Wandi, N.Ninkina, S.Millership, S.J.M.Williamson, P.A.Jones and V.L.Buchman (2010) Absence of a-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice. Neurobiology of Aging, 31, 796–804
- J.Burré, M.Sharma, T.Tsetsenis, V.Buchman, M.Etherton and T.C.Südhof (2010) a-Synuclein promotes SNARE-complex assembly in vitro and in vivo. Science, 329, 1663-1667
- B.Greten-Harrison, M.Polydoro, M.M.Tomita, L.Diao, A.M.Williams, E.H.Nie, N.Tian, P.E.Castillo, V.L.Buchman and S.Chandra (2010) abg-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Proc. Natl. Acad. Sci. USA, 107, 19573-19578
- S.Anwar, O.Peters, S.Millership, N.Ninkina, N.Doig, N.Connor-Robson, S.Threlfell, G.Kooner, R.M.Deacon, D.M.Bannerman, J.P.Bolam, S.S.Chandra, S.J.Cragg, R.Wade-Martins and V.L.Buchman (2011) Functional alterations to the nigrostriatal system in mice lacking all three members of the synuclein family. Journal of Neuroscience, 31, 7264-7274
- O.Peters, S.J.Millership, T.A.Shelkovnikova, I.Soto, L.Keeling, A.Hann, N.Marsh-Armstrong, V.L.Buchman and N.Ninkina (2012) Selective pattern of motor system damage in gamma-synuclein transgenic mice mirrors the respective pathology in amyotrophic lateral sclerosis. Neurobiology of Disease, in press