You could say that the Human Genome Project missed 99 percent of the genes in the adult body.
That’s because it didn’t sequence genes belonging to the vast communities of bacteria that normally live on and in us.
Now, a $1.45 million grant from the W.M. Keck Foundation will help fill this gap by funding a School of Medicine project that will develop new approaches for isolating, sequencing and analyzing the genomes of “friendly” bacteria that inhabit the intestine and that will identify the natural metabolic products that they synthesize in their native gut habitats.
The grant supports a project led by Jeffrey I. Gordon, M.D., director of the Center for Genome Sciences (CGS) and the Dr. Robert J. Glaser Distinguished University Professor and head of the Department of Molecular Biology and Pharmacology.
It reflects a partnership between his lab, the lab of Sean R. Eddy, Ph.D., associate professor of genetics, and members of the University’s Genome Sequencing Center.
The CGS is an innovative, interdepartmental, interdisciplinary enterprise strategically placed next to the Genome Sequencing Center. It is a major facet of the University’s BioMed 21 initiative, which aims to translate genomic science into patient care.
The CGS plays a catalytic role in helping devise new ways to translate the genetic data obtained from genome sequencing projects to allow researchers to better understand the evolution and diversity of life on Earth, as well as help create new methods to diagnose and treat patients with common and uncommon diseases.
Gordon views the human gut as a bioreactor programmed with at least 800 species of bacteria.
“Fortunately, these microbes endow us with key metabolic functions that we have not had to evolve on our own,” he said.
Gordon and his colleagues have shown that intestinal bacteria allow calories to be harvested from otherwise indigestible components of the diet.
These microbes also regulate the amount of extracted energy stored in fat cells.
The implication is that variations in the composition of gut microbial communities among different people may influence predisposition to obesity and obesity-related disorders such as diabetes and heart disease.
Unfortunately, comprehensive analysis of these microbial communities, in health and in disease, has been hampered because the majority of gut bacteria are difficult or impossible to grow and study outside of the intestine.
With the Keck Foundation’s support, the researchers will create new techniques for harvesting microbial communities along the length of the intestine and sequencing the genomes of new species, without having to culture them in test tubes.
They are also developing new computational methods for mining genome sequence data so bacterial species can be more rapidly and accurately classified.
A large, publicly accessible database will be established that provides detailed molecular information about the gut ecosystem for researchers.
The researchers also aim to directly identify the products of bacterial metabolism in the intestine and to characterize previously unknown compounds that regulate the properties of the microbial community and human physiology.
“We very grateful to the Keck Foundation, which has committed itself to funding high-risk projects designed to overcome key obstacles in emerging fields in science so that rapid progress can be made,” Gordon said.
“Its support of our studies of the genomic and metabolic foundations of mutually beneficial (symbiotic) relationships between microbes and humans will allow light to be shed on this previously mysterious interior world.”
The Keck Foundation, established in 1954 by the late W.M. Keck, founder of the Superior Oil Co., focuses its grants on pioneering efforts in the areas of medical research, science and engineering.
“Our objective is to understand how the human body functions as a carefully woven fabric of interacting species,” Gordon said.
“Ultimately, such understanding promises to provide new ways of fortifying health and preventing or treating a variety of diseases both inside and outside of the gastrointestinal tract.”