The association between a host and its microbiome is of central importance for life-history and evolutionary potential of the interacting organisms. Yet, we still have comparatively little understanding of the exact selective processes and resulting evolutionary consequences of these interactions. Adaptation to environmental stress may be facilitated through the interaction, for example if microbes enable the host to survive a harmful environmental condition and thereby the entire association of interacting organisms, the metaorganism, is able to persist. This beneficial interaction is likely to rely on the metabolic competences of the involved organisms and the exchange of nutrients and other substances. A better understanding of both the evolutionary processes and the underlying molecular and metabolic basis may be obtained with the help of an experimentally accessible host system. The model nematode Caenorhabditis elegans provides such a system. This nematode is associated with a speciesrich community of bacteria, most of which can also be easily maintained in culture.
In the first funding period, we established that an important function of the C. elegans microbiota is protection against pathogens. Based on omics approaches and metabolic network models, we further found that the individual members of the microbial community vary in their metabolic activities, thereby influencing key aspects of the host-microbiome interaction, for example colonization ability of the bacteria and C. elegans population growth.
Based on these insights, the overarching objectives of the A1 project in the second funding period will be to enhance our understanding of the evolution of microbiota-mediated protection against pathogen stress and the molecular and metabolic processes involved.
We will (1) experimentally test the influence of the microbiome on evolutionary adaptation of the C. elegans metaorganism to pathogens (A1.1, PI Schulenburg),
(2) study the molecular basis of microbiota-mediated protection against pathogens using functional genetics (A1.2, PI Dierking), and
(3) assess which metabolic pathways mediate the interaction between C. elegans and its microbiome during evolutionary adaptation and immune protection (A1.5, PI Kaleta).
The A1 PIs have complementary research competences (HS: evolution and ecology of C. elegans; KD: C. elegans immunity and signalling; CK: modelling of C. elegans and microbial metabolism), which will be combined across the subprojects. The proposed project is thus one of the first to experimentally test the role of the microbiome on evolutionary adaptation, using evolution experiments combined with omics, functional genetics, and metabolic modelling approaches. It is one of the very few to provide in-depth information on the genetic and molecular basis of distinct types of microbiota-mediated immune protection. It is also one of the first to explore and experimentally validate the interconnectivity of host and microbiome metabolic networks and its consequences for the resulting phenotypes.
This project exploits the advantages of the C. elegans model for a controlled interdisciplinary research agenda, in order to disentangle cause-effect relationships that define the evolution and function of a metaorganism.