1. The NIH Roadmap and the Human Microbiome Project Francis S. Collins, M.D., Ph.D. National Human Genome Research Institute April 22, 2007

2. The NIH Roadmap Program Roadmap projects were initiated in 2003, and are funded from a central NIH source (the “common fund”) Characteristics: –Must be truly transforming –Must require participation of NIH as a whole, and address a gap that no single IC or entity outside NIH is likely to fill –Ideally must provide a benefit by placing the outcome of the project in the public domain –Must be in need of development in “incubator space” in order to jump start the field

3. Three Themes for Roadmap 1.0 New Pathways to Discovery Re-engineering the Clinical Research Enterprise Research Teams of the Future

4. Re-engineering the Clinical Research Enterprise Public-Private Partnerships High-risk Research Interdisciplinary Research Nanomedicine Bioinformatics and Computational Biology Structural Biology Building Blocks, Biological Pathways and Networks Molecular Libraries and Imaging Implementation Groups New Pathways to Discovery Research Teams of the Future Clinical Enterprise Initiatives within Roadmap 1.0

5. The NIH Roadmap Program Roadmap projects were initiated in 2003, and are funded from a central NIH source (the “common fund”) Characteristics: –Must be truly transforming –Must require participation of NIH as a whole, and address a gap that no single IC or entity outside NIH is likely to fill –Ideally must provide a benefit by placing the outcome of the project in the public domain –Must be in need of development in “incubator space” in order to jump start the field A new competition for projects (“Roadmap 1.5”) is currently underway, with funding anticipated to start in FY08

6. Roadmap 1.5: What areas might be included in an HMP Proposal? Sequencing of a set of reference genomes from specified body sites (possibly, oral, intestinal, nasal/pharyngeal, urogenital, skin) Deep metagenomic sequencing of those sites to explore microbial complexity and the question of whether there is a core microbiome

7. Roadmap 1.5: What areas might be included in an HMP Proposal? Demonstration projects to test whether changes in the human microbiome can be related to human health –Multiple tissue sites, environmental factors, and disease states Technology development -- for example, efficient technology to purify genomic DNA from single microbial cells Development of bioinformatics tools for analysis and data handling

8. Roadmap 1.5: What areas might be included in an HMP Proposal? Data analysis and coordination effort for the entire project, to enhance the utility of the data for the biomedical research community, and to coordinate international efforts Data repository Resource repository to store samples, starting material, DNA, etc. ELSI projects, if needed, to explore challenges unique to the HMP endeavor

9. Human Microbiome Project: Context and Timeline

11. Potential for coordination of the HMP on several levels International coordination — potential EC, Japanese and Chinese projects Coordination of analysis in different projects Interagency coordination to develop technologies and data standards that can be used in all metagenomics projects Interagency cooperation on storage of cultured organisms and metagenomic samples