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)
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Prokaryotic Cell and Molecular Biology Study Section (PCMB)
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Chang, Michael
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University of Wisconsin Madison
Schools of Medicine
United States
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Heath-Heckman, Elizabeth A C; Gillette, Amani A; Augustin, René et al. (2014) Shaping the microenvironment: evidence for the influence of a host galaxin on symbiont acquisition and maintenance in the squid-Vibrio symbiosis. Environ Microbiol 16:3669-82
Studer, Sarah V; Schwartzman, Julia A; Ho, Jessica S et al. (2014) Non-native acylated homoserine lactones reveal that LuxIR quorum sensing promotes symbiont stability. Environ Microbiol 16:2623-34
Kremer, Natacha; Schwartzman, Julia; Augustin, René et al. (2014) The dual nature of haemocyanin in the establishment and persistence of the squid-vibrio symbiosis. Proc Biol Sci 281:20140504