Here we genome again

The Human Microbiome Project, dubbed the ‘Second Human Genome Project,’ poses more complexities

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BOSTON—The 108th meeting of the American Society for Microbiology here in early June provided a bit of a kickoff for fleshing out the Human Microbiome Project launched by the National Institutes of Health (NIH) at the end of last year.

Considered by some to be the "Second Human Genome Project," the Human Microbiome Project and its associated issues and considerations took center stage at the Boston meeting, with scientists there—both speakers and participants—sharing their thoughts about how to best carry out such studies. The conference's emphasis on metagenomics made it an ideal venue to get people excited about the Human Microbiome Project, says Claire Fraser-Liggett, director of the University of Maryland's Institute for Genome Sciences and one of the speakers at the event—her topic being the "Metagenomics of Human Microbiota."

"It's clearly the beginning of a new, large international effort," Fraser-Liggett says. But while many researchers have started comparing human microbiome research efforts to the Human Genome Project, there are significantly larger challenges in store for this project and thus NIH and others will have to work hard to keep things on track. Perhaps most importantly, finding a defined endpoint for the microbiome project will be more difficult than was the case with the Human Genome Project.
But the effort needs to be made despite the challenges, asserts Dr. Elias A. Zerhouni, director of the NIH, because while microorganisms make up only about one percent to two percent of the body's mass, they play huge roles in both maintaining our health and causing illness. Despite this, little is known about the role these bacteria, fungi and other microbes play in human health and disease.

"The human microbiome is largely unexplored," Zerhouni notes. "It is essential that we understand how microorganisms interact with the human body to affect health and disease. This project has the potential to transform the ways we understand human health and prevent, diagnose and treat a wide range of conditions."

Fraser-Liggett emphasized that because this project is more complex than even the Human Genome Project, the earliest efforts need to take into consideration the optimum sampling strategies—from type to number of samples to specific methods used—in addition to other experimental design issues. She notes, for example, that 16S rDNA-based analyses are useful but far from sufficient for gaining a complete view of microbiomes.

"It's critical that functional analysis go hand-in-hand with sequencing projects," Fraser-Liggett says. "Sequencing alone will not give you the necessary information."

What makes the project worth pursuing now is the new sequencing technology that will help to drive down costs for a project like this, says George Weinstock, associate director of the Genome Center at Washington University and professor of genetics at the Washington University School of Medicine. But even so, some of the other challenges remain in getting to some of the microbes, especially those in the gut, as well as development of improved automated methods for gene predictions and improvements in performing annotation.

Part of the NIH's Roadmap for Medical Research, the Human Microbiome Project will award a total of $115 million to researchers over the next five years. Initially, researchers will sequence 600 microbial genomes, completing a collection that will total some 1,000 microbial genomes. Other microbial genomes are being contributed to the collection by individual NIH institutes and internationally funded projects. DDN

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