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.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Research Project (R01)
Project #
Application #
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Zou, Sige
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Hawaii
Organized Research Units
United States
Zip Code
Kremer, Natacha; Koch, Eric J; El Filali, Adil et al. (2018) Persistent Interactions with Bacterial Symbionts Direct Mature-Host Cell Morphology and Gene Expression in the Squid-Vibrio Symbiosis. mSystems 3:
Koehler, Sabrina; Gaedeke, Roxane; Thompson, Cecilia et al. (2018) The model squid-vibrio symbiosis provides a window into the impact of strain- and species-level differences during the initial stages of symbiont engagement. Environ Microbiol :
Peyer, Suzanne M; Kremer, Natacha; McFall-Ngai, Margaret J (2018) Involvement of a host Cathepsin L in symbiont-induced cell death. Microbiologyopen 7:e00632
Bongrand, Clotilde; Ruby, Edward G (2018) Achieving a multi-strain symbiosis: strain behavior and infection dynamics. ISME J :
Nawroth, Janna C; Guo, Hanliang; Koch, Eric et al. (2017) Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome. Proc Natl Acad Sci U S A 114:9510-9516
Chen, Fangmin; Krasity, Benjamin C; Peyer, Suzanne M et al. (2017) Bactericidal Permeability-Increasing Proteins Shape Host-Microbe Interactions. MBio 8:
Pan, Shu; Nikolakakis, Kiel; Adamczyk, Paul A et al. (2017) Model-enabled gene search (MEGS) allows fast and direct discovery of enzymatic and transport gene functions in the marine bacterium Vibrio fischeri. J Biol Chem 292:10250-10261
Thompson, Luke R; Nikolakakis, Kiel; Pan, Shu et al. (2017) Transcriptional characterization of Vibrio fischeri during colonization of juvenile Euprymna scolopes. Environ Microbiol 19:1845-1856
Peyer, Suzanne M; Heath-Heckman, Elizabeth A C; McFall-Ngai, Margaret J (2017) Characterization of the cell polarity gene crumbs during the early development and maintenance of the squid-vibrio light organ symbiosis. Dev Genes Evol 227:375-387
Aschtgen, Marie-Stephanie; Wetzel, Keith; Goldman, William et al. (2016) Vibrio fischeri-derived outer membrane vesicles trigger host development. Cell Microbiol 18:488-99

Showing the most recent 10 out of 39 publications