Bacteria constitute the majority of the world's biomass and are responsible for most bioconversion on the planet. Bacterial pathogens, on the other hand, present major threats to human health, causing numerous infectious diseases in humans. Moreover, bacteria also serve as model organisms for us to understand fundamental biological processes, especially at the molecular and cellular levels. It is thus of paramount importance to understand how molecules coordinate and interact inside bacterial cells to support life processes. In bacteria, life processes take place in a small volume of <1

Public Health Relevance

In this project, we propose to determine a quantitative, high-resolution map of cellular architecture of E. coli with single-molecule sensitivity, nanometer-scale spatial resolution and molecular specificity of each individual gene, and to profile changes of this architecture in response to environmental conditions with a set of bioimaging and systems biology tools. This system-wide view of bacterial architecture with ultimate sensitivity and resolution will not only advance fundamental microbiology and cell biology, but may also suggest new therapeutic targets for bacteria-based infectious diseases. The new high-sensitivity, high-resolution imaging techniques and proteomic analysis tools developed here will also have broad applications to other areas of biomedical research.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM096450-03
Application #
8325097
Study Section
Special Emphasis Panel (ZRG1-BCMB-A (51))
Program Officer
Lewis, Catherine D
Project Start
2010-09-30
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$810,990
Indirect Cost
$296,145
Name
Harvard University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Wang, Siyuan; Su, Jun-Han; Beliveau, Brian J et al. (2016) Spatial organization of chromatin domains and compartments in single chromosomes. Science 353:598-602
Moffitt, Jeffrey R; Pandey, Shristi; Boettiger, Alistair N et al. (2016) Spatial organization shapes the turnover of a bacterial transcriptome. Elife 5:
Wang, Chong; Han, Boran; Zhou, Ruobo et al. (2016) Real-Time Imaging of Translation on Single mRNA Transcripts in Live Cells. Cell 165:990-1001
Chen, Kok Hao; Boettiger, Alistair N; Moffitt, Jeffrey R et al. (2015) RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348:aaa6090
Sigal, Yaron M; Speer, Colenso M; Babcock, Hazen P et al. (2015) Mapping Synaptic Input Fields of Neurons with Super-Resolution Imaging. Cell 163:493-505
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Chen, Huiyi; Shiroguchi, Katsuyuki; Ge, Hao et al. (2015) Genome-wide study of mRNA degradation and transcript elongation in Escherichia coli. Mol Syst Biol 11:808
Chong, Shasha; Chen, Chongyi; Ge, Hao et al. (2014) Mechanism of transcriptional bursting in bacteria. Cell 158:314-26
Wang, Siyuan; Moffitt, Jeffrey R; Dempsey, Graham T et al. (2014) Characterization and development of photoactivatable fluorescent proteins for single-molecule-based superresolution imaging. Proc Natl Acad Sci U S A 111:8452-7
Zhao, Ziqing W; Roy, Rahul; Gebhardt, J Christof M et al. (2014) Spatial organization of RNA polymerase II inside a mammalian cell nucleus revealed by reflected light-sheet superresolution microscopy. Proc Natl Acad Sci U S A 111:681-6

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