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Researchers at Washington University in St. Louis have shown that obese mice have a different proportion of one microorganism to another one in their gut than lean mice do. Could this someday lead to a treatment to battle obesity in humans? It might, and this promising discovery points to why the National Institute of Health’s (NIH) newest “roadmap” initiative is so important.

With the Human Genome Project under its belt, NIH’s Roadmap for Medical Research now turns to the trillions of microorganisms that live in the human body. To better understand the role of the bacteria, fungi, virus, archaea, phage and other microorganisms that compose 1 to 2 percent of the body’s mass, NIH announced late last year the Human Microbiome Project with a goal of sequencing 600 microbial genomes over the next five years. The total number of microbial genomes sequenced is expected to be closer to 1,000, thanks to contributions expected from individual NIH institutes and internationally funded projects.

“It’s another one of those kinds of projects that adds to our understanding of the total human organism. There are people who say it is the completion of the human genome because it is the set of organisms that act with us intimately.

It’s an important and obvious step, but it’s not the only one,” explained Jane Peterson, associate director of the NIH National Human Genome Research Institute’s Division of Extramural Research. She holds a doctorate from the University of Colorado in molecular, cellular and developmental biology.

Explaining how a better understanding of microbial communities could improve human health, Peterson gave this example: “There are reasons to believe that, particularly with some of the inflammatory bowel diseases, the human genome the bugs reside in have a lot to do with how the immune system reacts to those bugs.”

The Human Microbiome Project will focus on five areas of the body: the digestive tract, the female vagina, the skin, nasal passages and the oral cavity.

Researchers will use laboratory technologies, some very new, to characterize the microbial communities present in samples taken from human volunteers. “In many of these cases, you can’t isolate some of these bugs because we don’t know how to grow them. You have to look at the mixture because you can’t just get one bug,” Peterson said. “By necessity, we’ve been pushed to looking at the complex mixture. That, of course, allows you to look at a community.” Traditionally, microbiology has focused on the study of individual species, thus making it difficult to develop and inventory all the microbes in and on the body. Yet their growth is dependent on a specific natural environment. That’s why this examination is so important to the understanding of human microbiomes, she explained.

Peterson said the project is divided generally into two parts. The first is the control group -— samples from healthy people with results serving as “a data resource.” The second is samples from volunteers who suffer from various maladies “and how they stack up against healthy sites,” she said.

The examination of healthy volunteers has already begun. The NIH awarded $8.2 million to four sequencing centers, which will start laying the groundwork for the project. The objective of this initial work is to sequence the genomes that already have been isolated. Also, the researchers will begin recruiting more healthy volunteers who will donate samples from the five body regions. Peterson called this initiative “a jump-start project.” The four one-year-award institutions are Baylor College of Medicine, Houston; Washington University; the Broad Institute of the Massachusetts Institute of Technology and Harvard University; and the J. Craig Venter Institute in Rockville, Md.

NIH is requesting proposals for projects and intends to fund up to 10 demonstrations projects in the first year. “The ones that look like they are going to succeed will be scaled up in the subsequent years,” Peterson said. At the most, five will have funding continued. “The best of all worlds would be that they would all be great and that we don’t have enough money to do them and maybe then we’ll be able to find funding elsewhere,” she said.

The projects selected will begin in February 2009, and $115 million is available over the five years of the project.

In related news, the NIH announced in January the 1000 Genomes Project, an effort to sequence the genomes of at least 1,000 people from around the world. The idea is to create the most detailed and medically useful picture to date of human genetic variation. While any two humans are more than 99 percent the same at the genetic level, that small fraction that is the variable might help explain susceptibility to disease, response to drugs or reaction to environmental factors. Genetic variants could be associated with a host of risks, such as diabetes, coronary artery disease, prostate and breast cancer, rheumatoid arthritis and inflammatory bowel disease.



March 2008

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