BiophysicsStructural biologyNeurodegenerative desiasesSynchrotron x-ray diffraction and x-ray spectroscopy,
Victor Streltsov has received Master’s Degree in Physical Chemistry and Physics at Mendeleev University of Chemical Technology of Russia (MUCTR, Moscow) and Moscow State University (1982), and PhD in Physics and Mathematics with specialisation in Crystallography and Crystal Physics at MUCTR (1986). His has been further trained in the Biomolecular Structures Laboratory (Acad BK Vainstein) of the Institute of Crystallography of Russian Academy of Science and the University of Western Australia (UWA Postdoctoral award, Crystallography Centre, Dr EN Maslen). In 2002 he joined CSIRO and was a stream (group) leader in the Neurodegenerative disease theme of the CSIRO Preventative Flagship running projects in diagnostic, imaging and neuroprotective agents, using structure-based design methods closely collaborating with the Florey Institute of Neuroscience and Mental Health (Prof CL Masters), The University of Melbourne. He was a Visiting Researcher/Professor at Chalmers University of Technology (Sweden) and JSPS fellow at Tokyo Institute of Technology (Japan). He was an Honorary Professorial Fellow at Florey Institute and Physics Department of the University of Melbourne. He is currently conducting structural studies of proteins involved in neurodegenerative diseases at Florey Institute and a specially appointed Professor at the Tokyo Institute of Technology (Tokyo, Japan) with Prof H. Kawaji’s group. Prof Streltsov has а broad expertise in synchrotron structural studies of various types of materials from minerals, small and macro-molecules to cells, tissues and animal brains in the fields of charge density, protein crystallography, x-ray spectroscopy, small/wide angle x-ray scattering, x-ray imaging and cryo-EM.
It will extend my collaboration with Tokyo Tech initiated many years ago. It will also help to establish contacts with other researchers and major research centers in Japan. My current structure-based research in neurodegeneration will benefit from interdisciplinary research conducted at WHRI with investigators from different areas of specialized knowledge and skill.
Normal and abnormal pathways in Amyloid-beta and Tau-protein.
Collaborative research plan involves synchrotron x-ray studies (crystallography, spectroscopy) and electron microscopy (cryo-EM) of amyloid-β (Aβ) peptide and Tau-protein oligomers to better understand the process of filament formation and fibril elongation (nanostructures), with focus on effects of metals (Fe, Cu, Zn) on amyloid aggregation. Aggregation leads to an increase in thermal stability linked to the typical conformation transition to a β-hairpin and a cross-β structure. Amyloid proteins by nature are display a high level of thermal stability, due to the thermo-dynamically favourable state of the aggregated form.
Within this context we propose to investigate thermodynamic properties of fibril and filament materials in collaboration with the Materials and Structures Laboratory (MSL) at the Tokyo Tech WHRI. MSL aims to create innovative materials with outstanding properties and functions through interdisciplinary research efforts merging the fields of inorganic materials, metals and (bio)organic materials.
Proposed studies of Aβ and Tau proteins are significant and important, since these proteins play a major role in developing Alzheimer’s disease (AD). AD is a progressive neurodegenerative disorder that is characterized by the presence of Aβ fibrils and tau filaments in the brain. AD is the most common cause of dementia (up to 80%) and its prevalence is increasing in Japan and around the world and there are currently no disease modifying drugs for its treatment.
- Periods: 2019-2022
- Members: Florey Institute of Neuroscience and Mental Health and School of Physics of the University of Melbourne (Australia), Materials and Structures laboratory of Tokyo Tech and WHRI.
Amyloid-betaTau-proteinAmyloid-beta structureTau-filament formation
Research Scientist, Institute of Crystallography, Moscow, Russian Federation
The University of Western Australia Postdoctoral Research Fellow, The UWA Crystallography Centre, Perth, Australia
Senior Research Fellow at the UWA Crystallography Centre, Perth, Australia
Senior Research Scientist, Project Leader, CSIRO Molecular and Health Technologies Division, Melbourne. Australia
Principal Research Scientist, Stream Leader, CSIRO Preventative Health Flagship and Materials Sciences and Engineering Division, and CRC for Mental Health, Melbourne, Australia
Honorary Professorial Fellow, The Florey Institute of Neuroscience and Mental Health, and School of Physics, The University of Melbourne
Principal Researcher at The Florey Institute of Neuroscience and Mental Health
Specially Appointed Professor, Institute of Innovative Research, Tokyo Institute of Technology
Distinguished Visiting Scientist Fellowship, Chalmers University of Technology, Göteborg, Sweden
|1999 & 2002|| |
JSPS (Japanese Society for Promotion of Science) and Australian Academy of Science (AAS) Visiting Fellowships, Tokyo Institute of Technology, Japan
The CSIRO Chairman’s Medal and Award for insulin receptor structure study
The CSIRO Medal and Award for structural studies of amyloid-β oligomers in Alzheimer’s disease
JSPS Visiting Fellowship, Nagoya Institute of Technology, Japan
Streltsov VA, Belokoneva EL, Tsirelson VG, Hansen NK. Multipole analysis of the electron density in triphylite, LiFePO4, using X-ray diffraction data (1993) Acta Crystallographica Section B: Structural Science 49 (2), 147-153
Streltsov VA, Varghese JN, Carmichael JA, Irving RA, Hudson PJ & Nuttall SD, Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell surface receptor. Proc. Natl. Acad. Sci. USA (2004), 101, 12444-12449
McKern NM, Lawrence MC, Streltsov VA, Lou MZ, Adams TE, Lovrecz GO, Elleman TC, Richards KM, Bentley JD, Pilling PA, Hoyne PA, Cartledge KA, Pham TM, Lewis JL, Sankovich SE, Stoichevska V, Da Silva E, Robinson CP, Frenkel MJ, Sparrow LG, Fernley RT, Epa VC, Ward CW. (2006) Structure of the insulin receptor ectodomain reveals a folded-over conformation. Nature 443: 218-221
Streltsov VA, Titmuss S, Epa V, Barnham K, Masters C, Varghese JN (2008) The structure of the Amyloid β-peptide high affinity Copper II binding site in Alzheimer’s Disease” Biophys. J. 95(7): 3447–3456
Streltsov VA, Varghese JN, Masters CL, Nuttall SD (2011) Crystal Structure of the Amyloid-β p3 Fragment Provides a Model for Oligomer Formation in Alzheimer’s Disease, J. Neuroscience, 31: 1419-1426
Kim J-H, Resende R, Wennekes T, Chen H-M, Bance N, Buchini S, Watts AG, Pilling P, Streltsov VA, Petric M, Liggins R, Barrett S, McKimm-Breschkin JL, Niikura M, Withers SG (2013) Mechanism-based covalent neuraminidase inhibitors with broad spectrum influenza antiviral activity. Science, 340, 71-75
Streltsov VA, Ekanayake RSK, Drew SC, Chantler CT, Best SP (2018) Structural Insight into Redox Dynamics of Copper Bound N-truncated Amyloid-β Peptides from in situ X-ray Absorption Spectroscopy. Inorg Chem., 57(18), 11422-11435
Streltsov VA, Luang S, Peisley A, Varghese JN, Ketudat Cairns JR, Fort S, Hijnen M, Tvaroška I, Ardá A, Jiménez-Barbero J, Alfonso-Prieto M, Rovira C, Mendoza F, Tiessler-Sala L, Sánchez- Aparicio S-E, Rodríguez-Guerra J, Lluch JM, Maréchal J-D, Masgrau L, Hrmova M (2019) Nature Communications, accepted.