Human Microbiome Project awards funds for technology development, data analysis and ethical research

Bethesda 16 October 2008The National Institutes of Health (NIH) have introduced the first awards for the Human Microbiome Project, which will lay a foundation for efforts to explore how complex communities of microbes interact with the human body to influence health and disease. The funding, estimated to be up to approximately $21,2 million, will support the development of innovative technologies and computational tools, co-ordination of data analysis and an examination of some of the ethical, legal and social implications of human microbiome research.

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The human microbiome consists of all of the DNA, or genomes, of all the micro-organisms present in or on the human body. Launched in 2007 as part of the NIH's Roadmap for Medical Research, the Human Microbiome Project is a five-year effort that will produce a resource for researchers who are seeking to use information about the microbiome to improve human health.

"Today marks the beginning of efforts by researchers to put in place the framework for understanding how micro-organisms interact with our bodies to affect health and disease", stated NIH Director Elias A. Zerhouni, M.D. "Developing new and more cost-effective technologies will be essential to applying knowledge about the human microbiome to the prevention, diagnosis and treatment of a wide array of conditions."

Initially, researchers plan to sequence 600 microbial genomes, completing a collection that will total some 1000 microbial genomes. The remaining microbial genomes are being contributed to the collection by individual NIH institutes and internationally funded projects. Those data will then be used to characterize the microbial communities present in samples taken from healthy human volunteers. The samples will be collected from five areas of the body: the digestive tract, the mouth, the skin, the nose and the vagina.

After researchers generate profiles of microbial communities in healthy people, they will conduct demonstration projects to sample the microbiomes of volunteers with specific diseases. This will allow researchers to see if there are changes in the microbiome at particular body sites that correlate to specific diseases.

Traditionally, microbiology has focused on the study of individual species of micro-organisms as isolated units, making it difficult to inventory all of the microbes in and on the human body. Because microbial growth is dependent upon a specific natural environment, it often is difficult to recreate microbe-host interactions in the laboratory.

Recent advances in DNA sequencing technologies have accelerated a process called metagenomic sequencing. Instead of focusing on the genomes of individual microbes, metagenomic sequencing analyses all of the DNA of all of the microbes found within a sample.

Much of the work being funded in the first round of the Human Microbiome Project is aimed at improving and refining the identification of microbes that constitute the microbiome. Computational tools will also be developed to optimize the assembly of sequencing data to infer the location and function of genes, as well to classify microbial species.

"The development of new tools and technologies is central to our ability to meet the goals of the Human Microbiome Project", stated Alan Krensky, M.D., director of the Office of Portfolio Analysis and Strategic Initiatives, which oversees the NIH Roadmap for Medical Research. "An exceptional amount of information will be generated by this project and we need robust technologies and analytical tools that are equal to the task."

The principal investigators who will develop new technologies and computational tools, their approximate funding levels and their areas of research are:

  • Technology Development
    • Eugene B. Chang, M.D., The University of Chicago Medical Center; $410.000 (2 years); Technologies for the Discovery of Novel Human Colonic Mucosal-Associated Microbes.
    • Andre Marziali, Ph.D., Boreal Genomics Inc., North Vancouver, British Columbia; $770.000 (2 years); DNA Extraction to Normalize Species Representation.
    • David Relman, M.D., Stanford University, Palo Alto, California; $1,6 million (3 years); Optimization of a Microfluidic Device for Single Bacterial Cell Genomics.
    • Thomas Schmidt, Ph.D., Michigan State University, East Lansing and Vincent Young, M.D., Ph.D., University of Michigan, Ann Arbor; $1,3 million (3 years); Cultivation and Characterization of the Microaerobes from the Mucosa of the Gastrointestinal Tract.
    • Kun Zhang, Ph.D. and Yu-Hwa Lo, Ph.D., University of California, San Diego; $1,8 million (3 years); An Integrated Lab-On-Chip System for Genome Sequencing of Single Microbial Cells.
  • Computational Tools
    • Daniel Haft, Ph.D., J. Craig Venter Institute, Rockville, Md.; $1,6 million (3 years); Algorithmically Tuned Protein Families, Rule Base and Characterized Proteins.
    • Robin Knight, Ph.D., University of Colorado at Boulder; $1,1 million (3 years); New Tools for Understanding the Composition and Dynamics of Microbial Communities.
    • Mihai Pop, Ph.D., University of Maryland, College Park; $780.000 (3 years); Assembly and Analysis Software for Exploring the Human Microbiome.
    • Yuzhen Ye, Ph.D., Indiana University, Bloomington; $770.000 (3 years); Fragment Assembly and Metabolic Species Diversity Analysis for the Human Microbiome.

The NIH also awarded a co-operative agreement of approximately $9,9 million over five years to establish the Human Microbiome Project Data Analysis and Co-ordination Center, which will be led by Owen White, Ph.D., University of Maryland School of Medicine, Baltimore. As a community resource project, all data generated by the Human Microbiome Project will be deposited in the Data Analysis and Co-ordination Center as well as other public databases, including those supported by the National Center for Biotechnology Information, part of the National Library of Medicine.

Scientists from around the globe have met in Heidelberg, Germany, on 16 October 2008 and have formed the International Human Microbiome Consortium (IHMC). The IHMC will generate a shared data resource from international projects that will be made freely available to the global scientific community. Research organisations from all nations supporting similar research efforts are invited to become participants.

Leaders from the National Institutes of Health (NIH), part of the United States Department of Health and Human Services, signed a letter of intent in September with the European Commission (EC) officially agreeing to combine the data from the NIH Human Microbiome Project and the EC Metagenomics of the Human Intestinal Tract (MetaHIT) project. Both projects, which are already under way, will contribute an initial set of microbial genomes to the IHMC.

Current participants in the IHMP include:

  • Australia: Commonwealth Scientific and Industrial Research Organization
  • Canada: Canadian Institute of Health Research and Genome Canada
  • China: Ministry Of Science and Technology
  • Europe: European Commission
  • United States: National Institutes of Health

The IHMC will be guided by a steering committee made up of one representative from each country's research funding agency, as well as a representative from each scientific project. The steering committee is charged with maintaining standards related to quality assurance of data, co-ordination of microbial strains for complete genome sequencing projects, data access and release and informed consent, in addition to other issues which need the committee's input.

The IHMC is open for membership from any researchers who agree to the consortium's principles, which include:

  • open, free and rapid data release in accordance with donor consent forms
  • common quality standards for data
  • sharing of protocols and informed consent documents
  • sharing of information about progress of each project
  • a common publication policy

Each participating research group plans to focus on describing different body sites and diseases, while the United States and the European Commission will also contribute to a reference set of completely sequenced microbial genomes.

Data generated by IHMC projects will be made available through the NIH Human Microbiome Project Data Analysis and Co-ordination Center, led by Owen White, Ph.D., University of Maryland School of Medicine, Baltimore and an equivalent centre at the European Molecular Biology Laboratory (EMBL), led by Peer Bork, Ph.D. The data will also be distributed to other public databases, including those supported by the National Center for Biotechnology Information, part of the National Library of Medicine.

In addition, the Human Microbiome Project awarded approximately $1,2 million over three years to Richard Sharp, Ph.D. and Ruth Farrell, M.D., of the Cleveland Clinic to examine some of the ethical, legal and social implications of human microbiome research. Specifically, Dr. Sharp and his team will study patient perceptions about probiotic - beneficial bacteria - therapies and other potential clinical applications of human microbiome research.

The Human Microbiome Project is part of the NIH Roadmap for Medical Research and is managed by the National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research, National Institute of Diabetes, Digestive and Kidney Diseases and National Human Genome Research Institute, all part of NIH. The Roadmap is a series of initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone, but which the agency as a whole can address to make the biggest impact possible on the progress of medical research.

The National Institutes of Health (NIH) includes 27 Institutes and Centers and is a component of the United States Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. More information about the Human Microbiome Project is available at the NIH Roadmap website.


Leslie Versweyveld

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