Mailing and shipping address: Center for Genome Sciences Campus Box 8510 4444 Forest Park Blvd., Room 5401 St. Louis, MO  63108

Phones & Faxes: Office Phone:  314-362-0269 Lab Phone:  314-362-3963 Lab Fax:  314-362-2156 J. Gordon Office Phone: 314-362-7243 J. Gordon Fax: 314-362-7047

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Research Abstract:

Symbiotic or mutually beneficial relationships between microbes and animals are a dominant theme of life on our microbe-dominated planet. We are no exception: the total number of microbes that colonize our body surfaces exceeds our total number of somatic and germ cells by 10-fold. The majority of our symbionts reside in our intestines (10-100 trillion bugs), where they provide us with traits we have not had to evolve on our own. In this sense, we should view ourselves as a composite of species, both bacterial, archaeal and human, our genetic landscape as a summation of the genes embedded in our own human genome and the genes embedded in the genomes (‘microbiome’) of our microbial partners (the latter outnumber the former by at least 100-fold), and our ‘metabolic features as an amalgamation of human and microbial attributes.

We are interested in the following questions: What are the genomic and metabolic foundations of our mutually beneficial relationships with microbes? Do all humans share an identifiable core ‘microbiome’? How different are our microbiomes? Should differences in our microbiomes be viewed, along with our immune and nervous systems, as features of our biology that are affected by our individual environmental exposures? How is the human microbiome evolving as a function of our changing diets, lifestyle, and biosphere? How can we use this knowledge to intentionally manipulate our microbial communities to optimize their performance in the context of an individual, or population? To identify the foundations of these symbiotic relationships, we are sequencing the genomes of 100 representative members of the human gut microbial community so that we can make predictions about what attributes they possess that we have not had to evolve on our own.

We use germ-free model organisms (normal and genetically engineered mice), colonized with single or defined communities of sequenced wild-type (or mutant) bacterial and archaeal species that normally reside in the human gut, to simultaneously monitor host and microbial responses to colonization. We employ a variety of techniques, including metagenomics (sequencing whole microbial community DNA to define its gene content), functional genomics, and mass-spec-based metabolomics, so that we can compare and contrast the composition of the gut microbial community and its microbiome in normal mice and mice that serve as models for common human diseases. We are taking the insights we glean from mouse models and validating them in humans, including mono- and di-zygotic twin pairs and their mothers. One key question we are addressing is whether differences in our gut microbial ecology affect our pre-disposition to obesity.

Finally, we use germ-free normal and genetically manipulated mice to identify host and microbial factors that allow Helicobacter pylori, a bacterium that colonizes the stomachs of 50% of humans, to operate along the continuum between mutualism and pathogenicity. This project focuses on interactions between H. pylori and gastric stem cells, and includes comparative genomic studies of clinical isolates from patients followed over time, who do, or do not go progress to gastric neoplasia.

 

Keywords: functional and comparative genomics, genome analysis (microbial), ecology (symbiosis, ecogenomics), computational biology, systems biology, gut development, gut stem cells