Crystal elegance reveals viral solutions
Dr Fasseli Coulibaly has found beauty beneath the surface of the most brutal human diseases. His enchantment with the elegance of virus architecture has led to a pioneering study of crystallised insect virus proteins, which could provide the first vaccines to protect against complex diseases such as HIV.
Fasseli is using robust protein microcrystals, which originally occur in insect viruses, to develop a novel platform of viral vaccine delivery. The microcrystals could improve antigen delivery because they can carry the kind of complex vaccines required to fight pathogens such as HIV.
Fasseli says the microcrystals are also very stable, meaning they are well suited to developing countries where refrigeration is not guaranteed.
The research, funded by the Bill and Melinda Gates Foundation, is being undertaken in partnership with a Burnet Institute team led by Associate Professor Rosemary Ffrench.
It is based on Fasseli’s 2007 breakthrough made at the University of Auckland with Peter Metcalf and Japanese collaborator Hajime Mori, which has been documented in Nature. He used X-ray crystallography to identify the structure of miniscule insect virus proteins for the first time. X-ray crystallography uses synchrotron light to analyse protein crystals in three dimensions.
X-ray crystallography is also a fundamental part of his research to better understand smallpox and hepatitis C viruses. The Australian synchrotron is essential to this work. Its intense X-ray light beams are already being used to reveal how smallpox virus protein crystals are assembled. This could potentially lead to smallpox antivirals.
“It is like switching on a light in a dark room,” Fasseli says. “If you manage to crack the structure you can understand the virus strategies in their most intimate detail, which can ultimately lead to the development of new drugs.”
Unlike synthetically produced protein crystals, which can take years to develop, Fasseli’s insect protein virus can spontaneously crystallise. This increases the protein’s stability, making it ideal for use in developing countries – to which Fasseli has a personal connection.
“My father’s family is from Mali in West Africa, so it is satisfying to do something that could have an impact there,” the French expatriate says.
Fasseli and his team are also developing crystals for a hepatitis C project with Dr Heidi Drummer’s Burnet Institute laboratory, aimed at understanding how the virus invades host cells. This has implications for the design of new vaccines and antivirals.
Besides the potential health benefits that flow from his work, Fasseli says he is drawn to the simple elegance of this microscopic world.
“Viruses are very inventive at finding ways of going around cell defences, so this elegance in the viral processes is what I like,” he says. “And as for the structural biology, what I really love is what we see. We reveal molecular structures for the first time, but the crystals themselves are beautiful. I love seeing them.”
Commentary: structural virology , Supervision: X-ray crystallography, molecular virology, nanotechnology
Gouklani, H., Bull, R.A., Beyer, C., Coulibaly, F.J., Gowans, E.J., Drummer, H.E., Netter, H.J., White, P.A., Haqshenas, G., 2012, Hepatitis C virus nonstructural protein 5B is involved in virus morphogenesis, Journal Of Virology [P], vol 86, issue 9, American Society for Microbiology, USA, pp. 5080-5088.
Chiu, E., Coulibaly, F.J., Metcalf, P., 2012, Insect virus polyhedra, infectious protein crystals that contain virus particles, Current Opinion in Structural Biology [P], vol 22, issue 2, Elsevier Ltd * Current Opinion Journals, UK, pp. 234-240.
Coulibaly, F.J., 2012, Les polyedres viraux: armures cristallines des virus d'insectes, Virologie [P], vol 16, issue 3, John Libbey Eurotext, France, pp. 134-147.
Coulibaly, F.J., Lassalle, E., Baker, H.M., Baker, E.N., 2012, Structure of phosphoserine aminotransferase from Mycobacterium tuberculosis, Acta Crystallographica Section D-Biological Crystallography [P], vol 68, issue 5, Wiley-Blackwell Publishing, Inc., USA, pp. 553-563.
Kang, H.J., Coulibaly, F.J., Proft, T., Baker, E.N., 2011, Crystal structure of Spy0129, a Streptococcus pyogenes class B sortase involved in pilus assembly, PLoS ONE [P], vol 6, issue 1 (Art. No: e15969), Public Library of Science, USA, pp. 1-11.
Hyun, J., Accurso, C., Hijnen, M., Schult, P., Pettikiriarachchi, A., Mitra, A., Coulibaly, F., 2011, Membrane remodeling by the double-barrel scaffolding protein of poxvirus, Plos Pathogens [P], vol 7, issue 9 (e1002239), Public Library of Science, USA, pp. 1-14.
Gutsche, I., Coulibaly, F., Voss, J., Salmon, J., D'Alayer, J., Ermonval, M., Larquet, E., Charneau, P., Krey, T., Megret, F., Guittet, E., Rey, F., Flamand, M., 2011, Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 108, issue 19, National Academy of Sciences, USA, pp. 8003-8008.
Volkoff, A., Jouan, V., Urbach, S., Samain, S., Bergoin, M., Wincker, P., Demettre, E., Cousserans, F., Provost, B., Coulibaly, F.J., Legeai, F., Beliveau, C., Cusson, M., Gyapay, G., Drezen, J., 2010, Analysis of virion structural components reveals vestiges of the ancestral ichnovirus genome, Plos Pathogens [P], vol 6, issue 5 (e1000923), Public Library of Science, USA, pp. 1-10.
Coulibaly, F.J., Chevalier, C., Delmas, B., Rey, F.A., 2010, Crystal structure of an aquabirnavirus particle: Insights into antigenic diversity and virulence determinism, Journal Of Virology [P], vol 84, issue 4, American Society for Microbiology, USA, pp. 1792-1799.
Law, R.H.P., Lukoyanova, N., Voskoboinik, I., Caradoc-Davies, T.T., Baran, K., Dunstone, M.A., D'Angelo, M., Orlova, E.V., Coulibaly, F.J., Verschoor, S., Browne, K.A., Ciccone, A., Kuiper, M.J., Bird, P.I., Trapani, J.A., Saibil, H.R., Whisstock, J.C., 2010, The structural basis for membrane binding and pore formation by lymphocyte perforin, Nature [P], vol 468, issue 7322, Nature Publishing Group, UK, pp. 447-451.
Ijiri, H., Coulibaly, F.J., Nishimura, G., Nakai, D., Chiu, E., Takenaka, C., Ikeda, K., Nakazawa, H., Hamada, N., Kotani, E., Metcalf, P., Kawamata, S., Mori, H., 2009, Structure-based targeting of bioactive proteins into cypovirus polyhedra and application to immobilized cytokines for mammalian cell culture, Biomaterials [P], vol 30, issue 26, Elsevier BV, The Netherlands, pp. 4297-4308.
Coulibaly, F.J., Chiu, E., Gutmann, S., Rajendran, C., Haebel, P.W., Ikeda, K., Mori, H., Ward, V.K., Schulze-Briese, C., Metcalf, P., 2009, The atomic structure of baculovirus polyhedra reveals the independent emergence of infectious crystals in DNA and RNA viruses, Proceedings Of The National Academy Of Sciences O..., vol 106, issue 52, National Academy of Sciences, USA, pp. 22205-22210.
Letzel, T., Coulibaly, F.J., Rey, F.A., Delmas, B., Jagt, E., van Loon, A.A.M., Mundt, E., 2007, Molecular and structural bases for the antigenicity of VP2 of infectious bursal disease virus, Journal of Virology, vol 81, issue 23, American Society for Microbiology, USA, pp. 12827-12835.
Kang, H.J., Coulibaly, F.J., Clow, F., Proft, T., Baker, E.N., 2007, Stabilizing isopeptide bonds revealed in gram-positive bacterial pilus structure, Science, vol 318, issue 5856, American Association for the Advancement of Science, USA, pp. 1625-1628.
Coulibaly, F.J., Chiu, E., Ikeda, K., Gutmann, S., Haebel, P.W., Schulze-Briese, C., Mori, H., Metcalf, P., 2007, The molecular organization of cypovirus polyhedra, Nature, vol 446, issue 7131, Nature Publishing Group, UK, pp. 97-101.
Hyun, J., Coulibaly, F.J., Turner, A.P., Baker, E.N., Mercer, A.A., Mitra, A.K., 2007, The structure of a putative scaffolding protein of immature poxvirus particles as determined by electron microscopy suggests similarity with capsid proteins of large icosahedral DNA viruses, Journal of Virology, vol 81, issue 20, American Society for Microbiology, USA, pp. 11075-11083.
Coulibaly, F.J., Chevalier, C., Galloux, M., Da Costa, B., Lepault, J., Delmas, B., Rey, F., 2006, The structural relations between birnavirus and other icosahedral RNA viruses, Virologie, vol 10, issue 3, John Libbey Eurotext, France, pp. 233-235.
Coulibaly, F.J., Chevalier, C., Gutsche, I., Pous, J., Navaza, J., Bressanelli, S., Delmas, B., Rey, F.A., 2005, The birnavirus crystal structure reveals structural relationships among icosahedral viruses, Cell, vol 120, issue 6, Cell Press, USA, pp. 761-772.
Ohtsuka, Y., Nakai, D., Coulibaly, F.J., Metcalf, P., Mori, H., 2010, Mutations of cypovirus polyhedrin and applications of polyhedra to protein nanocontainers, Nanotech Conference & Expo 2010, NSTI, USA, pp. 292-295.
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