Prof Vladimir Buchman - MD PhD
1. Studies of synuclein family functions and their role in neurodegeneration
Expression of gamma-synuclein in sensory and motoneurons of E12.5 mouse embryo.
Gamma-synuclein in motor axonx and nerve terminals (adult mouse neuromuscular junction)
Patterns and dynamics of expression of all three members of synuclein family, alpha-, beta- and gamma-synuclein, suggest that these proteins should be involved in differentiation of specific populations of CNS and PNS neurons but physiological function(s) of all three synucleins is still elusive. At the moment the emphasis of our studies of this protein family is on animal models of synucleins dysfunction - knock-out (including double and triple knock-outs), transgenic and knock-in mice. Histology, primary cultures, behavioural tests and biochemical methods are used for characterisation of already generated mouse lines and production of new lines is in progress.
2. Regulation of intracellular signalling by Ruk proteins
Intracellular localisation of various GFP-Ruk isoforms expressed in COS7 cells.
Dynamics of Rukl/CIN85-induced structures Quicktime movie:
Multiple isoforms of Ruk protein, also known as CIN85, SETA or CD2BP3, are classic adaptor molecules able to interact with multiple protein partners and regulate many intracellular processes, including endocytosis, rearrangement of cytoskeleton and apoptotic cell death. Currently our studies are focused on effects of Ruk isoforms on membrane trafficking and intracellular signalling pathways. Our experimental approaches range from protein-protein interaction studies in vitro to functional studies in vivo, mainly in cell cultures with Tet-inducible expression of Ruk isoforms or targeted downregulation of isoform expression using siRNA.
3. Functions of d4 protein family
Two members of the d4 family in the developing mouse cerebellum.
Recently we have demonstrated that all members this family of presumptive transcription modulators involved in determination of cell fate interact in vitro with certain proteins and phospholipids. We use various model systems to investigate biological relevance of these interactions. We have also produced knock-outs of two neurospecific members of the family, neuro-d4 and cer-d4, and now characterising phenotypes of these single as well as double knock-out mice.
Current Grant Support
- The Wellcome Trust, including a Programme Grant
- Association for International Cancer Research
Collaborators
Dr. Herman van der Putten - Novartis Pharma, Basel, Switzerland (synucleins and neurodegeneration)
Prof. Thomas Südhof - University of Texas Southwestern Medical Center at Dallas, USA (physiological function of synucleins)
Prof. Olaf Riess - University of Tübingen, Germany (physiological function of synucleins)
Prof. Alun Davies - Cardiff University (signal transduction pathways implicated in neuronal differentiation)
Prof. Ivan Gout - University College London (Ruk isoforms in intracellular signaling)
Dr. Hiroshi Sakuae - Kobe University, Japan (function of synucleins in non-neuronal tissues)
Dr. Katerina Papachroni - University of Athens, Greece (synucleins as markers of neurological diseases)
Prof. Masatoshi Maki - Nagoya University, Japan (Ruk isoforms in membrane trafficing)
Dr. Ludmila Drobot - Institute of Cell Biology, Lviv, Ukraine (Ruk isoforms in tumour cells)
Drs. Elena and Igor Korobko - Institute of Gene Biology, Moscow (intra- and intermolecular interactions of Ruk proteins; the role of MAK-V kinase in mouse development and physiology)
Drs. Ilja Mertsalov, Dina Kulikova and Olga Simonova - Institute of Gene Biology, Moscow (functional studies of d4 family members in mice and Drosophila)
Dr. Silke Sperling - Max Planck Institute for Molecular Genetics, Berlin, Germany (cer-d4 proteins in heart diseases)