CRC 1182 Talk – Prof. Dr. Buck Samuel (Baylor College of Medicine, Houston, USA) 17.08.2018
Invited guest speaker at the Biology Center of the Christian-Albrechts-University Kiel
Friday, August 17th 2018, 14:00
Conference room 4th floor
Am Botanischen Garten 11
As guest of the CRC 1182
Prof. Dr. Buck Samuel
(Baylor College of Medicine, Houston, USA)
“Cultivated relationships: genetic landscapes that shape C. elegans microbiome form and function”
Partnerships between animals and microbes are ancient and coevolved relationships are common and born out of mutual benefit. Proper establishment and maintenance of these relationships relies on strong lines of host-microbial communication. Our goal is to develop a comprehensive understanding of the host-microbial signaling pathways that regulate these processes. Toward this end, we employ the genetically tractable, high-throughput amenable and microbially ‘tuned’ nematode Caenorhabditis elegans. Microbiome acquisition by C. elegans appears also to be a deterministic process, whereby specific bacterial strains colonize the C. elegans gut — dominated by Enterobacteriaceae, Pseudomonadaceae, Xanthomonadaceae, Sphingomonadaceae, three Bacteroidetes families among several more rare potential ‘keystone’ families. Thus, we sought to define the host genetic factors that regulate acquisition of its natural microbiome.
To address this question, we first established a model microbiome of 68 bacterial isolates with >98% identify to core taxa from collaborative meta-analyses . We then examined the natural variation in colonization and composition of this model microbiome when given to 42 previously ‘germ-free’ wild C. elegans strains. Using a high-throughput gut colonization method that we developed, we observed host strain specific colonization levels over a 30 fold range with the lab-adapted N2 strain and 4 other wild strains among the most ‘poor controllers’ of colonization. As in the wild, 16S sequencing of animal guts over time demonstrated distinct separation of microbiome and bacterial lawns for the majority of the strains tested (~75%). Surprisingly, six strains (‘poor selectors’) appear to lack programs for deterministic selection as their gut microbiomes were comparable in composition to the lawn. No strains tested were defective in both selection and control, suggesting that C. elegans may exhibit complementary genetic programs for regulation of the microbiome by separate programs.
Using previously generated genomes of these 42 C. elegans strains , we sought to identify the genetic basis of the variation in microbiome control and composition. We employed a combination of conventional GWAS, allelic clustering and machine-learning based methodologies to identify candidate genetic regulators [512 for control; 499 for selection]. The majority are predicted to be intestinally expressed and responsive to microbes. Also, these candidates fall into highly conserved pathways common in other systems for microbiome regulation. Together, we establish C. elegans as a robust natural system for cataloguing the genetic pathways that regulate microbiome acquisition and identify a multitude of new regulators that are likely to be broadly conserved across the animal kingdom.