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4. Mihnea Bostina

Dr Mihnea Bostina

Research interests:

Structural biology, viral pathogenesis and molecular virology

Current research:

Our research interests are in understanding molecular architectures and relating those structures to their functional mechanisms. To do this, we are employing cryo-electron microscopy and electron tomography combined with image analysis techniques.

Lab group

Postgraduate students

Research projects

• Seneca Valley Virus

 Seneca Valley Virus (SVV) is a novel oncolytic RNA virus belonging to the Picornaviridae family. SVV has an exclusive tropism for cancer cells and has shown promising results in several clinical trials. Recently, the anthrax toxin receptor, ANTXR1, has been identified as the high-affinity cellular receptor for SVV in multiple cell types. Interestingly, this is the first example of a common shared receptor between a mammalian virus and a bacterial toxin. Our study of SVV follows several directions: i) the structural biology of SVV interaction with receptor and host antibodies; ii) the cellular remodeling induced by SVV infection, and iii) developing SVV for treatment of breast cancer.

• Bacteriophages

This project aims to describe the structures of several bacteriophages active against P. syringae pv. actinidiae, a re-emerging pathogen, which causes bacterial canker of kiwifruit (Actinidia sp.). The economic impact, and the development of resistance against antibiotics and copper sprays, has led to a search for alternative management strategies, such as devising bacteriophage cocktails active against this agricultural pathogen. (Collaboration with Peter Fineran)

• Iridovirus

Iridoviruses are large double-stranded DNA viruses infecting a range of insects.  They have an internal lipid membrane encapsidated into a fiber-covered icosahedral capsid. In special circumstances, the capsids self-assemble into crystal colloidal arrays refracting light in a limited wavelength domain. Understanding the architecture of the capsid in detail can be instrumental in controlling the formation of assembled arrays with desired optical properties important for photonic and material applications. The goal of this project is to obtain a high resolution structure of capsid and understand the role  played by capsid fibers in regulating the array formation. (Collaboration with Vernon Ward)

• Oryctes nudivirus is a natural pathogen to the rhinoceros beetle, a very important pest of coconut and oil palms throughout Southeast Asia and the Pacific Islands. The virus has been successfully used to control this pest and could become a sustainable and environmental-friendly tool to battle it if it is effectively produced, formulated, and applied in the field. (Collaboration with Gabriel Visnovski, University of Canterbury)

For details about Diploma, MSc or PhD projects, please contact me at mihnea.bostina@otago.ac.nz

Lab alumni

WonMo Kim (2018), Ana Rivera (2018), Sally Kim (2014-2018), Brian Tong (2015-2017), William Szabo (2016), Ryan Murphy-Dawes (2015), Chelsea Harris (2015), Danni Chen (2014), Mariya Yevstigneyeva (2014), Mike Strauss (2014).

Publications:

• McCarthy C, N Jayawardena, LN Burga^*, M Bostina^*. 2019. Developing Picornaviruses for Cancer Therapy. Cancers (Basel). 11(5). pii: E685.
• Bostina, M. 2019. Monoclonal antibodies point to Achilles’ heel in picornavirus capsid. PLOS Biology. doi:10.1371/journal.pbio.3000232
• Harland, DP, V Novotna, M Richena, S Velamoor, M Bostina, AJ McKinnon. 2019. Helical twist direction in the macrofibrils of keratin fibres is left handed. J Struct Biol. https://doi.org/10.1016/j.jsb.2019.04.007
• Watson, BNJ, RA Easingwood, B. Tong, M. Wolf, GPC Salmond, RHJ Staals, M Bostina^*, PC Fineran^*. 2019. Different genetic and morphological outcomes for phages targeted by single or multiple CRISPR-Cas spacers. Phil. Trans. R. Soc. B. 374(1772):20180090 
• Jayawardena, N, LN Burga, RA Easingwood, Y Takizawa, M Wolf*, M Bostina*. 2018. Structural basis for Anthrax Toxin Receptor 1 recognition by Seneca Valley Virus. PNAS. 13;115(46):E10934-E10940.
• Strauss, M, N Jayawardena, E Sun, RA Easingwood, LN Burga*, M Bostina*. 2017. Cryo-EM Structure of Seneca Valley Virus Procapsid. Journal of Virology 92(6):e01927-17.
• Miles L, LNBurga, E Gardner, MBostina, JT Poirier, C Rudin. 2017. Anthrax toxin receptor 1 (ANTXR1) is the cellular receptor for Seneca Valley Virus in neuroendocrine cancers. Journal of Clinical Investigation. 127(8):2957-2967.
• Fagerlund, RD, ME Wilkinson, O Klykov, A Barendregt, FG Pearce, SN Kieper, HWR Maxwell, A Capolupo, AJR Heck, KL Krause, M Bostina, RA Scheltema, RHJ Staals, PC Fineran. 2017. Spacer capture and integration by a type I-F Cas1:Cas2-3 CRISPR adaptation complex. PNAS. 14(26):E5122-E5128
• Basu, K., D Lajoie, T Aumentado-Armstrong, I Chen, RI Koning, B Bossy, M Bostina, A Sik, E Bossy-Wetzel, I Rouiller. 2017. Molecular mechanism of DRP1 assembly studied in vitro by cryo-electron microscopy. PLOS One 12(6):e0179397.
• Hampton, H.G., M.B. McNeil, T.J. Paterson, B. Ney, N.R. Williamson, R.A. Easingwood, M. Bostina, G.P.C. Salmond, and P.C. Fineran. 2016. CRISPR-Cas gene editing reveals RsmA and RsmC act through FlhDC to repress the SdhE flavinylation factor and control motility and prodigiosin production in Serratia. Microbiology. 162(6):1047-58
• Frampton RA, Acedo EL, Young VL, Chen D, Tong B, Taylor C, Easingwood RA, Pitman AR, Kleffmann T, M Bostina*, PC Fineran*. 2015. Genome, Proteome and Structure of a T7-Like Bacteriophage of the Kiwifruit Canker Phytopathogen Pseudomonas syringae pv. actinidiae. Viruses. 7(7):3361-79.
• Schoderboeck, L.,S. Riad, A.M. Bokor, H.E. Wicky, M. Strauss, M.Bostina, M.J. Oswald, R.M. Empson, S.M. Hughes. 2015. Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord. Gene Therapy. 22(5):357-64.
• Kalynych S., M. Cherney, M. Bostina, I. Rouiller, and M. Cygler. 2015. Quaternary structure of WzzB and WzzE polysaccharide copolymerases. Protein Science. 24(1):58-69
• Sverzhinsky A., L. Fabre, A. L. Cottreau, D. M. Biot-Pelletier, S. Khalil, M. Bostina, I. Rouiller, and J. W. Coulton. 2014. Coordinated rearrangements between cytoplasmic and periplasmic domains of the membrane protein complex ExbB-ExbD of Escherichia coli. Structure 22: 791-7.
• Schotte L., M. Strauss, B. Thys, H. Halewyck, D.J. Filman, M. Bostina, J.M. Hogle, and B. Rombaut. 2014. Mechanism of action and capsid stabilizing properties of VHHs with an in vitro anti-polioviral activity. Journal of Virology 88(8): 4403-13.
• Grishin, A.M., E. Ajamian, L. Tao, M. Bostina, L. Zhang, J-F. Trempe, R. Menard, I. Rouiller, and M. Cygler. 2013. Family of phenylacetyl-CoA monooxygenases differs in subunit organization from other monooxygenases. Journal of  Structural Biology 184(2):147-54.
• Strauss, M., H. C. Levy, M. Bostina, D. J. Filman, and J. M. Hogle. 2013. RNA transfer from poliovirus 135S particles across membranes is mediated by long umbilical connectors. Journal of Virology 87:3903-3914.
• Abedi, S., B. Karimi, F. Kazemi, M. Bostina, and H. Vali. 2013. Amorphous TiO2 coated into periodic mesoporous organosilicate channels as a new binary photocatalyst for regeneration of carbonyl compounds from oximes under sunlight irradiation. Organic & Biomolecular Chemistry 11:416-419.
• Kulczyk, A. W., B. Akabayov, S. J. Lee, M. Bostina, S. A. Berkowitz, and C. C. Richardson. 2012. An interaction between DNA polymerase and helicase is essential for the high processivity of the bacteriophage T7 replisome. Journal of  Biological Chemistry 287:39050-39060.
• Karimi, B., H. Behzadnia, M. Bostina, and H. Vali. 2012. A nano-fibrillated mesoporous carbon as an effective support for palladium nanoparticles in the aerobic oxidation of alcohols "on pure water". Chemistry 18:8634-8640.
• Grishin, A. M., E. Ajamian, L. Zhang, I. Rouiller, M. Bostina, and M. Cygler. 2012. Protein-protein interactions in the beta-oxidation part of the phenylacetate utilization pathway: crystal structure of the PaaF-PaaG hydratase-isomerase complex. Journal of  Biological Chemistry 287:37986-37996.
• Gopalakrishnan, G., P. T. Yam, C. Madwar, M. Bostina, I. Rouiller, D. R. Colman, and R. B. Lennox. 2011. Label-free visualization of ultrastructural features of artificial synapses via cryo-EM. ACS Chemical Neuroscience 2:700-704.
• Bostina, M., H. Levy, D. J. Filman, and J. M. Hogle. 2011. Poliovirus RNA is released from the capsid near a twofold symmetry axis. Journal of Virology 85:776-783.
• Levy, H. C., M. Bostina, D. J. Filman, and J. M. Hogle. 2010. Catching a virus in the act of RNA release: a novel poliovirus uncoating intermediate characterized by cryo-electron microscopy. Journal of Virology 84:4426-4441.
• Levy, H.C., M. Bostina, D.J. Filman, and J.M. Hogle. 2010. Cell Entry: a Biochemical and Structural Perspective. Chapter 6 in The Picornaviruses. 87-104. ASM Press Washington, DC. Edited by E. Ehrenfeld, E. Domingo, and R. Roos
• Burga, L. N., N. M. Tung, S. L. Troyan, M. Bostina, P. A. Konstantinopoulos, H. Fountzilas, D. Spentzos, A. Miron, Y. A. Yassin, B. T. Lee, and G. M. Wulf. 2009. Altered proliferation and differentiation properties of primary mammary epithelial cells from BRCA1 mutation carriers. Cancer Research 69:1273-1278.
• Bostina, M., D. Bubeck, C. Schwartz, D. Nicastro, D. J. Filman, and J. M. Hogle. 2007. Single particle cryoelectron tomography characterization of the structure and structural variability of poliovirus-receptor-membrane complex at 30 A resolution. Journal of Structural Biology 160(2):200-210.
• Peng, G., M. Bostina, Radermacher, I. Rais, M. Karas, and H. Michel. 2006. Biochemical and electron microscopic characterization of the F1F0 ATP synthase from the hyperthermophilic eubacterium Aquifex aeolicus. FEBS Letters 580:5934-5940.
• Raunser, S., W. Haase, M. Bostina, D. N. Parcej, and W. Kuhlbrandt. 2005. High-yield expression, reconstitution and structure of the recombinant, fully functional glutamate transporter GLT-1 from Rattus norvegicus. Journal of Molecular Biology 351:598-613.
• Bostina, M., B. Mohsin, W. Kuhlbrandt, and I. Collinson. 2005. Atomic model of the E. coli membrane-bound protein translocation complex SecYEG. Journal of Molecular Biology 352:1035-1043.
• Abdrakhmanova, A., V. Zickermann, M. Bostina, M. Radermacher, H. Schagger, S. Kerscher, and U. Brandt. 2004. Subunit composition of mitochondrial complex I from the yeast Yarrowia lipolytica. Biochimica et Biophysica Acta 1658:148-156.
• Zickermann, V., M. Bostina, C. Hunte, T. Ruiz, M. Radermacher, and U. Brandt. 2003. Functional implications from an unexpected position of the 49-kDa subunit of NADH:ubiquinone oxidoreductase. Journal of  Biological Chemistry 278:29072-29078.
• Peng, G., G. Fritzsch, V. Zickermann, H. Schagger, R. Mentele, F. Lottspeich, M. Bostina, M. Radermacher, R. Huber, K. O. Stetter, and H. Michel. 2003. Isolation, characterization and electron microscopic single particle analysis of the NADH:ubiquinone oxidoreductase (complex I) from the hyperthermophilic eubacterium Aquifex aeolicus. Biochemistry 42:3032-3039.