The long-term objectives of the proposed research are to understand the complex dialogue that occurs between humans and their microbiota, and how this molecular conversation supports their dynamic stability as the host matures. To achieve this goal requires a clear understanding of how these essential microbial communities form, how they function, and what role they play in the natural biological rhythms that characterize daily life. To help discover the rules underlying the complex interactions between the hundreds or thousands of microbial species present in and on the human body, scientists use simple model systems to provide a window into the fundamental principles by which different bacteria function with their host. One such model system is the light- organ symbiosis between the bioluminescent bacterium, Vibrio fischeri, and its squid host, Euprymna scolopes. A fundamental characteristic of this association is a profound daily rhythm in the relationship between the bacteria and the epithelial tissue with which they associate. Because this tissue is easily imaged, and is colonized by a single, genetically manipulable bacterial species, the symbiosis offers the rare opportunity to decipher, with high temporal and spatial resolution, the reciprocal molecular and biochemical dialogue that is essential for persistence of a natural symbiosis.
The specific aims of the proposed research are to (i) characterize the steps that allow the partners to initiate their rhythmic interaction, (ii) define how the development of metabolic cycling underlies this rhythm, and (iii) determine the molecular mechanisms (i.e., 'clocks') that drive evolutionarily conserved symbiotic rhythms.
These aims will be achieved by a combination of approaches including imaging and analysis of host-tissue remodeling, construction of bacterial mutants for probing colonization events, and tracking and probing the symbiosis as it is initiated, and as its rhythmic patterns develop from the immature into mature state.

Public Health Relevance

These studies represent the first analyses of the influence of bacterial partners on setting and maintaining the natural daily rhythms of the host. This work is relevant to human microbiome researchers, who will be able to use the rules discovered here to better focus their studies of maintaining a healthy state between humans and their microbiota.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Research Project (R01)
Project #
5R01OD011024-18
Application #
8693043
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Chang, Michael
Project Start
1996-09-30
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
18
Fiscal Year
2014
Total Cost
$497,118
Indirect Cost
$162,420
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Aschtgen, Marie-Stephanie; Lynch, Jonathan B; Koch, Eric et al. (2016) Rotation of Vibrio fischeri Flagella Produces Outer Membrane Vesicles That Induce Host Development. J Bacteriol 198:2156-65
Schwartzman, Julia A; Ruby, Edward G (2016) A conserved chemical dialog of mutualism: lessons from squid and vibrio. Microbes Infect 18:1-10
Bongrand, Clotilde; Koch, Eric J; Moriano-Gutierrez, Silvia et al. (2016) A genomic comparison of 13 symbiotic Vibrio fischeri isolates from the perspective of their host source and colonization behavior. ISME J 10:2907-2917
Aschtgen, Marie-Stephanie; Wetzel, Keith; Goldman, William et al. (2016) Vibrio fischeri-derived outer membrane vesicles trigger host development. Cell Microbiol 18:488-99
Nikolakakis, K; Monfils, K; Moriano-Gutierrez, S et al. (2015) Characterization of the Vibrio fischeri Fatty Acid Chemoreceptors, VfcB and VfcB2. Appl Environ Microbiol 82:696-704
Krasity, Benjamin C; Troll, Joshua V; Lehnert, Erik M et al. (2015) Structural and functional features of a developmentally regulated lipopolysaccharide-binding protein. MBio 6:e01193-15
Nikolakakis, K; Lehnert, E; McFall-Ngai, M J et al. (2015) Use of Hybridization Chain Reaction-Fluorescent In Situ Hybridization To Track Gene Expression by Both Partners during Initiation of Symbiosis. Appl Environ Microbiol 81:4728-35
Schwartzman, Julia A; Koch, Eric; Heath-Heckman, Elizabeth A C et al. (2015) The chemistry of negotiation: rhythmic, glycan-driven acidification in a symbiotic conversation. Proc Natl Acad Sci U S A 112:566-71
Singh, Priyanka; Brooks 2nd, John F; Ray, Valerie A et al. (2015) CysK Plays a Role in Biofilm Formation and Colonization by Vibrio fischeri. Appl Environ Microbiol 81:5223-34
Pan, Min; Schwartzman, Julia A; Dunn, Anne K et al. (2015) A Single Host-Derived Glycan Impacts Key Regulatory Nodes of Symbiont Metabolism in a Coevolved Mutualism. MBio 6:e00811

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