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Genome Architecture: Where Genomics and Nanotechnology Meet
By Nancy Touchette

The human genome map revealed that most genes are peppered unevenly throughout chromosomes in small clusters amid vast deserts of “junk” DNA. Now a diverse group of scientists is coming together to figure out why the genome is arranged the way it is and how its structure affects its function.

“In the nucleus, the genome is not just a long stretch of DNA,” says Timothy O’Brien of Jackson Laboratory in Bar Harbor, Maine. “It’s folded and looped and packaged with proteins. For the cell, this type of structure is going to matter a bunch.”

Chromosome 17 (green) and remaining DNA (blue) are compacted within a human fibroblast nucleus.

O’Brien, who studies the development of the embryo, became intrigued by the unusual arrangement of genes within the human genome. So he helped organize a meeting on the subject two years ago at Jackson Lab. That meeting, Advances in Nanostructural Genomics, brought together scientists from several worlds: genomics and genetics, biophysics, nanotechnology, and cell biology.

The meeting led to the formation of the Genome Architecture Consortium. The primary goal of the consortium is to bring together scientists who are not used to talking to each other but who are interested in understanding the three-dimensional structure of the genome.

Cell biologists have helped other scientists think about how DNA behaves in the context of the cell. And nanotechnologists have been instrumental in coming up with new techniques for studying the complex arrangements of DNA. For example, magnetic nanoparticles are being developed that can be injected into the nuclei of living cells, where they can probe small areas of the genome.

The consortium is already helping scientists who have different perspectives find common ground.

O’Brien, for example, thinks about DNA in terms of how it guides the development of the embryo. But biophysicists think of DNA as a long rod governed by repulsions and attractions between charged ions.

Initially, O’Brien was not interested in the biophysical properties of DNA. But then he realized that these properties dictate how DNA interacts with other molecules in the cell.

“Proteins coat the DNA, and it’s the proteins that regulate gene activity,” says O’Brien. “So it’s fundamental to understand these interactions to figure out how genes behave as part of a system.”

The consortium is actively encouraging collaborative ventures between researchers. O’Brien and other members co-authored a review article that recently appeared in Genome Research.

In addition, Jackson Laboratory, together with the University of Maine and the Maine Medical Center Research Institute, has launched a brand new Institute for Molecular Biophysics. The institute, funded by the National Science Foundation and located in Orono, Maine, aims to bridge the gap between biophysics and basic biomedical research.

The next Advances in Nanostructural Genomics meeting is scheduled for October 15, 2003, at Jackson Laboratory.

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O’Brien, T.P. et al. Genome function and nuclear architecture: from gene expression to nanoscience. Genome Research 13, 1029-1041 (June 2003).

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