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The broad interest of our lab is to understand how organelles are built and maintained in cells. We are particularly interested in the specialized organelle biogenesis, which takes place during viral infection. Most single strand RNA viruses hijack cellular membranes and transform the membrane surface into viral replication factories. Picornaviruses in particular, such as poliovirus and Coxsackievirus, fill up the cytoplasm of the host cell with vesiculo-tubular replication organelles, derived from cellular membranes, whose surfaces are studded with viral replication enzymes.
Experimental approaches to investigate viral replication have been primarily methods that disrupt subcellular organization and/or average information from macroscopic ensemble measurements of many millions of infected and non-infected cells. These approaches are limited because they provide either a glimpse of the replication events at a single time point; they disrupt native cellular organization and physiology; or provide only population ‘averaged’ information, which may not be representative of any one member. Using these conventional approaches it is difficult to address questions regarding the biogenesis and spatio-temporal dynamics of viral replication organelles over the course of infection. Live-cell imaging methodologies however, are particularly well suited because they allow one to observe the dynamics of viral nucleic acids, and viral and cellular machinery without perturbation of the spatial organization or temporal order of events.
The morphological changes undergone by picornavirus infected cells have been observed by electron microscopic methods for the past 50 years but biochemical analyses of how they are formed, what induces their formation etc. have been fruitless. Now for the first time, new tools in the form of live-cell imaging are available. Using a combination of live-cell time-lapse confocal microscopy and fluorescence correlation spectroscopy with fluorescent protein, lipid and nucleic acid reporters, we are investigating the mechanisms involved in building these unconventional organelles and identifying their unique properties, which facilitate viral RNA replication.
B.A. in Biology, Hunter College, 1992.
Ph.D. in Cell Biology, The Rockefeller University, 1998.
Altan-Bonnet, N., and Balla, T. (2012). Phosphatidylinositol 4-kinases: Hostages harnessed to build panviral replication platforms. Trends in Biochemical Sciences 37(7): 293-302.
Altan-Bonnet, N., and Steele-Mortimer, O. (2012). Cell-pathogen interactions (viruses and bacteria). Molecular Biology of the Cell 23(6): 978.
Hsu NY., Ilnytska O., Belov G., Santiana M., Chen YH., Takvorian PM., Pau C., van der Schaar H., Kaushik-Basu N., Balla T., Cameron CE., Ehrenfeld E., van Kuppeveld FJ., Altan-Bonnet N. (2010) Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell 141(5): 799-811.
Altan-Bonnet N., Altan-Bonnet G. (2009) Fluorescence correlation spectroscopy in living cells: A practical approach. Current Protocols in Cell Biology, Chapter 4.
Naslavsky N, McKenzie J, Altan-Bonnet N, Sheff D, Caplan S. (2009) EHD3 regulates early-endosome-to-Golgi transport and preserves Golgi morphology. Journal of Cell Science 122 (3): 389-400.
Guan D, Altan-Bonnet N, Parrott AM, Arrigo CJ, Li Q, Khaleduzzaman M, Li H, Lee CG, Pe'ery T, Mathews MB. (2008) Nuclear factor 45 (NF45) is a regulatory subunit of complexes with NF90/110 involved in mitotic control. Molecular and Cellular Biology 28(14):4629-4641.
Altan-Bonnet N. (2007) Imaging the Golgi apparatus in living mitotic cells. Methods in Molecular Biology 390:309-328.
Belov G., Altan-Bonnet N., Kovtunovych G., Jackson CL., Lippincott-Schwartz J., Ehrenfeld E. (2007) Hijacking components of the secretory pathway for replication of poliovirus RNA. Journal of Virology. Journal of Virology 81(2): 558–567.
Altan-Bonnet N., Sougrat R., Liu W., Snapp EL., Ward TH and Lippincott-Schwartz J. (2006) Golgi inheritance in mammalian cells is mediated through endoplasmic reticulum export activities. Molecular Biology of the Cell 17(2): 990–1005.
Altan-Bonnet N., Sougrat R., and Lippincott-Schwartz J. (2004) Molecular basis of Golgi biogenesis as a steady-state system. Current Opinions in Cell Biology. 16 (4): 364–372.
Altan-Bonnet N., and Lippincott-Schwartz J. (2004) The Golgi apparatus: structure, function and dynamics. The Biology of Cellular Organelles. (eds. C. Mullins) Landes Press.
Altan-Bonnet N., Polishchuk, R., Phair, RD., Weigert R., and Lippincott-Schwartz J (2003) A role for Arf1 in mitotic Golgi disassembly, chromosome segregation and cytokinesis. Proceedings of the National Academy of Sciences 100; 13314–13319.
Lippincott-Schwartz J., Altan-Bonnet N., Patterson GH (2003) Photobleaching and photoactivation: following protein dynamics in living cells. Nature Cell Biology 5: S7–S14.
Snapp, E. L., Altan, N. & Lippincott-Schwartz, J. (2003) Measuring protein mobility by photobleaching GFP-chimeras in living cells. Current Protocols in Cell Biology (eds Bonifacino, J., Dasso, M., Harford, J. B., Lippincott-Schwartz, J. & Yamada, K. M.) 21.1.1–21.1.23 John Wiley & Sons.
Griffis E, Altan N., Lippincott-Schwartz, J., Powers, M (2002) Nup98 is a mobile nucleoporin with transcription dependent dynamics. Molecular Biology of the Cell 13: 1282–1297.
Zaal, K., Smith, C.L., Polishchuk, R.S., Altan N., Cole, N., Ellenberg, J., Hirschberg, K., Presley, J., Roberts, T., Siggia, E., Phair, R., and Lippincott-Schwartz, J. (1999) Golgi membranes are absorbed into and re-emerge from the ER during mitosis. Cell 99: 589–601.