The Joint Center for Structural Genomics: exploration of the human gut microbiome

Ian Wilson

doi:10.1186/gb-2011-12-s1-i18

Abstract

For more than a decade, the Joint Center for Structural Genomics (JCSG) [1] has been at the forefront of developing tools and methodologies that allow the application of high-throughput structural biology to a broad range of biological and biomedical investigations. In the previous phases of the National Institutes of Health’s Protein Structure Initiative (PSI; 2000 to 2010) [2], we explored structural coverage of uncharted regions of the protein universe [3], as well as a single organism, allowing complete structural reconstruction of the metabolic network of Thermotoga maritima[4]. In the current phase (PSI: Biology; 2010 to 2015), the JCSG is leveraging its high-throughput platform to explore the structural basis for host-microbe interactions in the human microbiome. The emerging field of metagenomics has been particularly enlightening: the human gut microbiome sequencing projects have already uncovered fascinating new families and expansions of known families for adaptation to this environment. The gut microbiota is dominated by poorly characterized bacterial phyla, which contain an unusually high number of uncharacterized proteins that are largely unstudied. Their influence upon human development, physiology, immunity and nutrition is only starting to surface and is thus an exciting new frontier for structural genomics, where we can structurally investigate the contributions of these microorganisms to human health and disease. The JCSG is located at The Scripps Research Institute, the Genomics Institute of the Novartis Research Foundation, University of California at San Diego, the Sanford-Burnham Medical Research Institute and SSRL/Stanford University.

Highlights

Despite a decrease in the rate of mortality due to diarrhea in the past few decades, diarrhea remains one of the leading causes of childhood deaths worldwide, especially in developing countries
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Summary

Introduction

Despite a decrease in the rate of mortality due to diarrhea in the past few decades, diarrhea remains one of the leading causes of childhood deaths worldwide, especially in developing countries. Recent genome-wide association studies (GWAS) have identified allele T of a single nucleotide polymorphism (SNP), rs2294008, in the prostate stem cell antigen (PSCA) gene as a risk factor for bladder cancer [1,2]. A recent genome-wide association study (GWAS) of bladder cancer identified a single nucleotide polymorphism (SNP), rs11892031, within the UGT1A gene cluster on chromosome 2q37.1, as a novel risk factor. Genome-wide association studies (GWAS) of human complex disease have identified a large number of disease-associated genetic loci, which are distinguished by distinctive frequencies of specific single nucleotide polymorphisms (SNPs) in individuals with a particular disease These data do not provide direct information on the biological basis http://genomebiology.com/supplements/12/S1 of a disease or on the underlying mechanisms. There may be multiple paths in the de Bruijn graph that can yield sequences with optical maps that match the genome’s optical map, these paths all yield very similar sequences in most cases

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