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Kit Pogliano

Research

Our research is organized around three key themes:

  • Cellular organization and dynamics:  What are the design principles of bacterial cells?
  • Microbial interactions:  How are the outcomes of interspecies interactions determined? 
  • Chemical Cell Biology:  How do secreted metabolites and antibiotics affect bacterial cells?

Our toolkit
We take a multidisciplinary approach to our studies, using the tools of genetics, cell biology, proteomics, biochemistry, and we have recently added analytical chemistry to our toolkit. Our lab is fully equipped for molecular biology, genetics and for work with BSL2 pathogens. Our microscopy facility includes one dissecting stereomicroscope equipped for fluorescence and timelapse imaging as well as deconvolution microscopes equipped with growth chambers and microfluidic devices for time-lapse microscopy and lasers for photobleaching and total internal reflection microscopy. We have an HPLC apparatus for the analysis and purification of natural products, and more extensive equipment is available in the labs of our campus collaborators. We have ready access to excellent campus facilities that provide cutting edge equipment and analytical tools for protein and small molecule mass spectrometry, super resolution microscopy and sequencing, with excellent technical assistance available as needed. We also apply our imaging expertise to a variety of collaborative projects and enjoy the diversity these projects and visitors bring to our lab.

The SpollQ landmark protein (green) localizes into puncta surrounding the developing spore, here visualized using structured illumination microscopy.

Cellular organization and dynamics:  What are the design principles of bacterial cells?

The phagocytosis-like process of engulfment is a hallmark of endospore formation in Bacillus subtilis and its relatives. Engulfment provides a unique example of phagocytosis in a bacterium and it is an ideal system to study protein localization and dynamics as well as membrane movement and fission. Engulfment depends on three protein complexes, the DMP complex that degrades peptidoglycan, the Q-AH complex that provides a Velcro-like attachment between the two cells and the peptidoglycan biosynthetic complex.  Our goal is to elucidate the mechanisms by which bacterial cells mediate membrane movement and membrane fission, coordinate peptidoglycan degradation and synthesis, and how they complete membrane fission after engulfment and cell division.

B. subtilis (green) invading and destroying a neighboring bacterial colony (red).

What role do antibiotics play in microbial communities?

The vast majority of commercial antibiotics are derived from secreted bacterial natural products. However, despite the clinical importance of these molecules and the pressing need to discover new antibiotics, it remains unclear exactly what role these molecules play in nature. The secreted metabolome of B. subtilis contains a wide array of well-characterized antibacterial and antifungal compounds, providing an ideal starting point to elucidate the specific roles each play in interspecies interactions and development. Undomesticated B. subtilis strains have the ability to invade and destroy neighboring colonies or to form mixed biofilms in a more cooperative mode of growth. Our goal is to identify the genes and secreted metabolites that mediate interspecies interactions, using the tools of analytical chemistry and imaging mass spectrometry (in collaboration with Pieter Dorrestein) as well as genetics and cell biology.

B. subtilis cells before and after treatment with the cannibalism toxin SDP.

Chemical Cell Biology: How do secreted metabolites and antibiotics affect bacterial cells?

We have developed cell biological tools to characterize the cellular targets for secreted metabolites and antibiotics, in collaboration with Joe Pogliano. This approach, which we call cytological profiling, has allowed us to rapidly identify molecules that kill bacterial cells and to determine their likely mechanism of action.  It is remarkably specific, as we can discriminate between the cytological effects of molecules that dissipate either the pH or  or both components of the PMF, as well as the effects of a wide array of antibiotics with well-characterized activities. These studies provide insight into the mechanisms by which essential biological processes are coordinated to maintain the appropriate size and they have several biomedical applications.

Publications

  • Nonejuie P., M. Burkhart, K. Pogliano and J. Pogliano. (2013) Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules.Proc. Natl. Acad. Sci., USA, in press.
  • Fredlund, J., D. Broder, T. Fleming C. Claussin and K. Pogliano. (2013) The SpoIIQ landmark protein has different requirements for septal localization and immobilization.  Molecular Microbiology, 89:1053-1068.
  • Dedrick R.M., L.J. Marinelli, G.L. Newton, K. Pogliano, J. Pogliano and G.F. Hatfull. (2013) Functional requirements for bacteriophage growth:  gene essentiality and expression in Mycobacteriophage Giles.  Molecular Microbiology 88:577-589.
  • Tocheva, E.I., J. Lopez-Garrido, HV Hughes, J. Fredlund, E. Kuru, M.S. Vannieuwenhze, Y.V Brun, K. Pogliano and G. Jensen. (2013) Peptidoglycan transformations during Bacillus subtilis sporulation. Molecular Microbiology 88:673-686.
  • Pang, T., T.C. Fleming, K. Pogliano and R. Young. (2013) Visualization of pinholin lesions in vivo. Proc. Natl. Acad. Sci., USA110:E2054-E2063.
  • Nguyen DD, Wu C-H, Moree WJ, Lamsa A, Medema MH, Zhao X, Gavilan RG, Aparicio M, Atencio L, Jackson C, Ballesteros J, Sanchez J, Watrous J, Phelan VV, van de Wiel C, Kersten RD, Mehnaz S, De Mot R, Shank EA, Charusanti P, Nagarajan H, Duggan BM, Moore BS, Bandeira N, Palsson BØ, Pogliano K, Gutiérrez M, Dorrestein PC (2013) MS/MS networking guided discovery of molecule and gene cluster families. Proc. Natl. Acad. Sci., USA 110:E2611-2620.
  • Lamsa, A., W.-T. Liu, P.C. Dorrestein and K. Pogliano. (2012) The Bacillus subtilis cannibalism toxin SDP collapses the proton motive force and induces autolysis. Molecular Microbiology, 84:486-500.
  • Phelan, V.V., W.-T. Liu, K. Pogliano and P.C. Dorrestein. (2012) Microbial metabolic exchange:  the chemotype-phenotype link. Nature Chemical Biology 8:26-35.
  • Watrous, J., P. Roach, T. Alexandrov, B.S. Heath, J.Y. Yang, R.D. Kersten, M. van der Voort, K. Pogliano, H. Gross, J.M. Raaijmakers, B.S. Moore, J. Laskin, N. Bandeira and P.C. Dorrestein (2012) Mass spectral molecular networking of living microbial colonies. Proc. Natl. Acad. Sci., USA, 109: E1743-1752.
  • Yang, J.Y., V.V. Phelan, R. Simkovsky, J.D. Watrous, R.M. Trial, T.C. Fleming, R. Wenter, B.S. Moore, S.S. Golden, K. Pogliano and P.C. Dorrestein. (2012) A primer on agar-based microbial imaging mass spectrometry.  J. Bact., 194: 6023-6028
  • Eswaramoorthy, P., J.A. Gregory, J. Silverman, K. Pogliano, J. Pogliano, and K.S. Ramamurthi. (2011) Cellular architecture mediates DivIVA ultrastructure and regulates Min activity in Bacillus subtilis. mBIO 2(6) e00257-11
  • White, R., S. Chiba, J.S. Dewey, C. Savva, T. Pang, A. Holzenburg, K. Pogliano and R. Young (2011) Holin triggering in real time.  Proc. Natl. Acad. Sci., USA, 108:793-803.
  • Chiba, S., T. Kanamori, T. Ueda, Y. Akiyama, K. Pogliano and K. Ito. (2011) Recruitment of a species-specific arrest module to monitor different cellular processes.  Proc. Natl. Acad. Sci., USA, 108:6073-6078
  • Gonzalez, D. N.M. Haste, A. Hollands, T. Fleming, M. Hanby, K. Pogliano, V. Nizet, P.C. Dorrestein. (2011) Microbial competition between Bacillus subtilis and Staphyloccocus auereus monitored by imaging mass spectrometry.Microbiology, 157:2485-2492.
  • Liu, W.-T., Y.-L. Yang, Y. Xu, A. Lamsa, J. Yang, J. Ng, C.D. Ellermeier, P.D. Straight, P.A. Pevzner, J. Pogliano, K. Pogliano and P.C. Dorrestein. (2010) Imaging mass spectrometry of intraspecies metabolic exchange reveals the cannibalistic factors of Bacillus subtilis. Proc. Natl. Acad. Sci., USA, 107:16286-16290.
  • Gregory, J.A., E.C. Becker J. Jung, I. Tuwatananurak and K. Pogliano.  (2010) Tn5 assisted gene insertion technology (TAGIT), a tool for generating fluorescent fusion proteins, PLoS One 5:e8731.
  • Ito, K., S. Chiba and K. Pogliano. (2010) Divergent stalling sequences sense and control cellular physiology, BBRC 393:1-5.
  • Meyer, P., J. Gutierrez, K. Pogliano and J. Dworkin. (2010) Cell wall synthesis is necessary for membrane dynamics during sporulation of Bacillus subtilis. Molecular Microbiology 76:956-970.
  • Gutierrez, J., R. Smith, and K. Pogliano. (2010) SpoIID-mediated peptidoglycan degradation is required throughout engulfment during Bacillus subtilis sporulation. J. Bacteriology 192:3174-3186.
  • Fleming, T., J.Y. Shin, S.H. Lee, E.C. Becker, K.C. Huang, C. Bustamante and K. Pogliano. (2010) Dynamic SpoIIIE assembly mediates septal membrane fission during Bacillus subtilis sporulation.  Genes and Development 24:1160-1172.
  • Gregory, J.A., E.C. Becker J. Jung, I. Tuwatananurak and K. Pogliano.  (2010) Tn5 assisted gene insertion technology (TAGIT), a tool for generating fluorescent fusion proteins, PLoS One 5:e8731.
  • Chiba, S. A. Lamsa and K. Pogliano. (2009) A ribosome nascent chain sensor of membrane protein biogenesis in Bacillus subtilis, EMBO J. 28:3461-3475
  • Ptacin, J., M. Nollmann, E.C. Becker, N.R. Cozzarelli, K. Pogliano and C. Bustamante. (2008) Sequence-directed DNA export guides chromosome translocation during sporulation in Bacillus subtilis. Nature Structural and Molecular Biology 15:485-493.
  • Gregory, J.A., E.C. Becker and K. Pogliano. (2008) Bacillus subtilis MinC destabilizes FtsZ-rings at new cell poles and contributes to the timing of cell division. Genes and Development 22:3475-3488.

Biography

Kit Pogliano received her Ph.D. from the Department of Microbiology and Molecular Genetics at Harvard Medical School and was a Damon Runyon-Walter Winchell postdoctoral fellow at Harvard University. She is a recipient of the Searle Scholar and Beckman Young Investigator awards. Dr. Pogliano was named in 2009 as a Fellow in the American Academy of Microbiology.