May 01, 2007

Metagenomics project to sequence all the microbes of our bodies

The bacteria in the human body are very difficult to study, since only about 1 percent of them can be grown in the lab. Now a proposed new project to sequence all our microbial residents could change that. The human body has 10 times as many microbial cells as human cells. They're a vital part of our health, breaking down otherwise indigestible foods, making essential vitamins, and even shaping our immune system.

Thanks to ever-improving methods to sequence DNA, scientists can now analyze the genomes of entire microbial communities, a field known as metagenomics. By comparing microbial communities in people of different ages, origins, and health statuses, researchers hope to find out precisely how microorganisms prevent or increase risk for certain diseases and whether they can be manipulated to improve health.

Several metagenomics projects are under way or have been completed, including analysis of the microbes living in the human gut and on the skin. But a true snapshot of our microbial menagerie will require a massive effort, along the lines of the Human Genome Project. "Even though a microbial genome is one-thousandth the size of the human genome, the total number of microbial genes in [the human] body is much greater than human genes because you have so many different species," says Weinstock.

The National Institutes of Health (NIH) is now considering such a project. Metagenomics experts and government officials met last week to determine if the proposal, dubbed the human microbiome, will become an NIH "Roadmap" initiative. These NIH-wide programs identify major gaps in biomedical research and provide financial support on a much larger scale than typical grants. A final decision is expected this month.

Five topics that have been selected to be developed for further consideration as Major NIH Roadmap Initiative Proposals:

* Microbiome – The Microbiome is the full collection of microbes (bacteria, fungi, viruses, etc.) that naturally exist within the human body. Initiatives in this area would focus on developing a deeper understanding of these communities of microbes in order to determine how they affect human health.
* Protein Capture/Proteome Tools – The Proteome is the complete set of proteins in the body. Efforts in this area would support developing and making available to the scientific community high quality probes specific to every protein in the human and in desired animal models. This would allow the ability to characterize protein function in health and disease and to monitor the markers of a disease in order to deploy early prevention efforts and to identify potential therapeutic targets.
* Phenotyping services and tools – A human Phenotype is the total physical appearance and constitution of a person, often determined by multiple genes and influenced by environmental interactions. Initiatives in this area would encourage the development of resources to systematically catalog human phenotypes in an effort to characterize complex diseases and disorders.
* Inflammation as a common mechanism of disease – While significant breakthroughs have occurred in our understanding of inflammation, research is needed to further understand inflammatory processes. Because inflammation is broadly implicated in many diseases and conditions, this initiative would be valuable in uncovering as-yet-unknown immune mechanisms and mediators of inflammation as well as genetic factors, environmental triggers, and the relationship of inflammation to disease.
* Epigenetics – Epigenetics is the study of stable genetic modifications that result in changes in gene expression and function without a corresponding alteration in DNA sequence. The epigenome is a catalog of the epigenetic modifications that occur in the genome. Epigenetic changes have been associated with disease, but further progress requires the development of better methods to detect the modifications and a clearer understanding of factors that drive these changes.

Regenerative Medicine is being placed into more information gathering to determine next steps.