Recent developments in fluorescence microscopy geared for single-molecule detection, optical sectioning and three-dimensional data acquisition, used in combination with object-identification algorithms, now allow sufficient temporal and spatial resolution to visualize the sequential recruitment and intracellular traffic of proteins, lipids, and pathogens in living cells including viruses and bacteria. The Kirchhausen laboratory has a longstanding interest in understanding the mechanisms underlying entry of toxins, viruses and bacteria into cells, and how these processes relate to the organization and intracellular traffic of vesiculo-tubular membrane carriers. As part of this effort, we have devoted substantial efforts to developing an imaging suite containing state-of-the-art microscopes and supporting software suited for data collection and analysis with high spatial and temporal resolution. It is also a priority to maintain an imaging suite that is 100% accessible to all users, so that after initial training, any investigator can perform their work with total flexibility and independence. In this proposal we outline plans for a NERCE Imaging Core facility that will provide access to contemporary tools and expertise for live-cell and single molecule imaging aimed towards, but not limited to, quantitative descriptions of mechanisms of invasion for bacterial and viral pathogens into mammalian cells, of viral replication, and of molecular aspects related to toxin entry into cells.
The Imaging Core will enable New England investigators to observe molecular events involving the entry, replication and pathology of infectious agents into host cells using real-time live cell imaging. The results of these studies will identify critical steps in the infectious process that may be targets for antimicrobial therapy.
|Clark, Margaret J; Miduturu, Chandra; Schmidt, Aaron G et al. (2016) GNF-2 Inhibits Dengue Virus by Targeting Abl Kinases and the Viral E Protein. Cell Chem Biol 23:443-52|
|Russo, Brian C; Stamm, Luisa M; Raaben, Matthijs et al. (2016) Intermediate filaments enable pathogen docking to trigger type 3 effector translocation. Nat Microbiol 1:16025|
|Kirienko, Daniel R; Revtovich, Alexey V; Kirienko, Natalia V (2016) A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence. mSphere 1:|
|Taylor, Travis J; Diaz, Fernando; Colgrove, Robert C et al. (2016) Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector. Virology 496:186-93|
|Chou, Yi-ying; Cuevas, Christian; Carocci, Margot et al. (2016) Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor. J Virol 90:4494-510|
|Mellata, Melha; Mitchell, Natalie M; SchÃ¶del, Florian et al. (2016) Novel vaccine antigen combinations elicit protective immune responses against Escherichia coli sepsis. Vaccine 34:656-62|
|Helenius, Iiro Taneli; Nair, Aisha; Bittar, Humberto E Trejo et al. (2016) Focused Screening Identifies Evoxine as a Small Molecule That Counteracts CO2-Induced Immune Suppression. J Biomol Screen 21:363-71|
|Stone, Laura K; Baym, Michael; Lieberman, Tami D et al. (2016) Compounds that select against the tetracycline-resistance efflux pump. Nat Chem Biol 12:902-904|
|Balasubramanian, Anuradha; Manzano, Mark; Teramoto, Tadahisa et al. (2016) High-throughput screening for the identification of small-molecule inhibitors of the flaviviral protease. Antiviral Res 134:6-16|
|Vrentas, Catherine E; Moayeri, Mahtab; Keefer, Andrea B et al. (2016) A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection. J Biol Chem 291:21596-21606|
Showing the most recent 10 out of 401 publications