The complex and dynamic communities of microbes that are present on and within the human body (the human microbiota) are thought to profoundly influence human health in a variety of ways, through effects on human physiology, nutrition, immunity, and development. Studies on humans and vertebrate animal models have generated evidence that this is the case for some specific diseases and suggest that further studies in this area may be vital for the understanding, prevention, and treatment of many human diseases, as well as the maintenance of homeostasis. It is currently a challenge to even identify comprehensively the components of the human microbiota, although genomic approaches have greatly improved the feasibility of doing so. The study of the collective DNA (the human microbiome) of community members has been spurred by recent advances in DNA sequencing and other technologies;such technologies have created the new field of metagenomics (determining the DNA sequence of genomes from a mixed community of organisms). One issue associated with metagenomic studies is that analysis of mixed populations is extremely difficult due to the highly heterogeneous nature of the sample. To avoid this issue, efforts to isolate individual organisms from these mixed populations have been used. Unfortunately, obtaining sufficient quantities of pure, individual isolates is also a challenge. Growth of bulk cultures and purification of DNA for analysis is tedious and labor intensive, and many isolates are difficult, if not impossible, to culture. The utilization of whole-genome amplification methods on single-cell isolates to provide sufficient DNA for comprehensive downstream testing is a solution to this problem. To date, reliable whole-genome DNA amplification methods have failed to provide DNA suitable for analysis from trace samples due to reagent contamination, method sensitivity issues, and the generation of chimeric products that confuse analysis. As a collaborative effort between GE and the Broad Institute (a world leader in the implementation of new technologies to generate DNA sequence), the methodology developed will provide a process that can be used by high throughput sequencing facilities to completely characterize individual microbes using DNA sequencing, furthering the knowledge, and stimulating work, in this area.

Public Health Relevance

There is a growing desire to understand more about the relationship human beings have with the microorganisms growing in and on their bodies (the human microbiome). DNA sequencing of the entire genome of each organism is one method being used to gather precise information about these microorganisms. The team plans to develop a whole-genome DNA amplification method with single cell sensitivity that will enable high-throughput DNA sequencing of entire genomes to be performed from single cells, eliminating the requirement to purify and culture each isolate.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-IDM-M (50))
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Schloss, Jeffery
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General Electric Global Research Center
United States
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