Award Abstract #0333284
Microbial Genome Sequencing: Comparative Microbial Genome Analysis of the Human-Bacteroides Symbiosis

NSF Org:	EF Emerging Frontiers
Initial Amendment Date:	September 17, 2003
Latest Amendment Date:	September 17, 2003
Award Number:	0333284
Award Instrument:	Standard Grant
Program Manager:	Matthew Kane EF Emerging Frontiers BIO Directorate for Biological Sciences
Start Date:	November 1, 2003
Expires:	October 31, 2007 (Estimated)
Awarded Amount to Date:	$1993732
Investigator(s):	Jeffrey Gordon jgordon@wustl.edu (Principal Investigator) Richard Wilson (Co-Principal Investigator)
Sponsor:	Washington University School of Medicine 660 South Euclid Avenue Saint Louis, MO 63110 314/747-4134
NSF Program(s):	BE: NON-ANNOUNCEMENT RESEARCH
Field Application(s):
Program Reference Code(s):	BIOT, 9183, 7187
Program Element Code(s):	1629

ABSTRACT

A grant has been awarded to Drs. Jeffrey I. Gordon and Richard K. Wilson of Washington University in St. Louis to sequence the DNA of bacteria that normally reside in the human intestine. The adult human is home to a vast number of friendly bacteria: the total number exceeds the number of human cells in our body. The largest collection of microbes resides in the intestine (10-100 trillion organisms). The number of bacterial genes embedded in the genomes of this community of 500-1000 species is ~100 times greater than the number of genes in our human genome. The products of these bacterial genes provide essential metabolic capacities not fully evolved in our own genome, including the ability to break down otherwise indigestible nutrients. The current revolution in genomics provides an unprecedented opportunity to define how components of the normal intestinal bacterial community modulate features of human postnatal development and adult physiology. This grant focuses on a group of bacteria known as Bacteroides that account for ~25% of the total microbial population in the human intestine. The genomes of several members of Bacteroides will be sequenced to determine how they have become such successful members of the gut microbial community and to define their contributions to human biology. The genome of a member of another group of bacteria, Eubacterium, evolutionarily distant from Bacteroides but also prominently represented in the human intestine, will be sequenced to identify features common to successful symbionts.

One assumption prompting this analysis is that our bacterial partners have developed the capacity to synthesize novel chemical entities that help establish and sustain their mutually beneficial relationships, and that prospecting for these chemicals, and characterizing how they operate will suggest new ways to maintain our health and vigor. In a dynamic, densely populated ecosystem like the gut, exchange of genes between bacterial species can have important effects on bacterial evolution and physiology (e.g., propagation of antibiotic resistance). Therefore, studying the genomes of gut bacteria provides an opportunity to address general questions related to how environment affects development of species, the definition and meaning of their extinction within a community, and the mechanisms by which they cooperate to process otherwise inaccessible nutrients. Studying the molecular strategies employed by symbionts for defining scarcity in their environment, for managing access to crucial resources when they are limiting, and for making decisions about sharing goods to ensure societal stability may yield operating principles important to environmental engineers, ecologists, economists, business managers, and those who study, organize, and even govern our human communities.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Bäckhed, F., Ley, R.E., Sonnenburg, J.L., Peterson, D.A. Gordon,.  "Host-bacterial mutualism in the human intestine,"  Science,  v.307,  2005,  p. 1915.

Ley et al..  "Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine,"  Cell, 124: 837-848 (2006,  v.124,  2006,  p. 837.

Westover, B.P., Buhler, J.D., Sonnenburg, J. L. and Gordon, J. I..  "Operon prediction without a training set,"  Bioinformatics,  v.21,  2005,  p. 880.

Xu, J. and Gordon, J.I.  "MapLinker: a software tool that aids physical map-linked whole genome shotgun assembly,"  Bioinformatics,  v.21,  2005,  p. 1265.

Xu, J., Mahowald, M.A., Ley, R.E., Lozupone, C.A., et. al..  "Evolution of Symbiotic Bacteria in the Distal Human Intestine,"  PLoS Biology,  v.5,  2007,  p. 1574.


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