The 1990s may have been designated the 'Decade of the Brain', but they will also be remembered as the time when genomics came to the fore. This year, neuroscience and genomics teamed up in projects that promise to propel the study of the brain into the realm of 'big science'.
Working on Parkinson's disease? One of the projects that surfaced this year might provide you with a transgenic mouse that offers fluorescent neurons in key neural pathways. Another could offer you structural brain images along with DNA samples from patients. Still stuck for inspiration? Another project will map all of the active genes in the neural pathways of your choice.
One of the most exciting initiatives owes its existence to the world's fourth-richest man, Paul Allen, who co-founded the software giant Microsoft. In September, he announced the donation of US$100 million over five years to create the Allen Institute of Brain Science in Seattle, Washington. Its first endeavour will be to produce a comprehensive atlas of gene activity in the mouse brain.
This will be a huge task — two-thirds of the 30,000-or-so genes in the mouse are expressed in its brain. Indeed, the project could generate petabytes of data — the same order of magnitude as all of the information currently held on the Internet. No wonder, then, that the Allen Institute has hired Mark Boguski, one of the world's foremost bioinformaticians, as its founding director.
The Allen Brain Atlas picks up from another project with similar goals: the Brain Molecular Anatomy Project (BMAP), launched by the US National Institutes of Health in 1998. “It was too early,” says Boguski. “Back then we didn't even know how many genes there were.” And whereas BMAP would have taken decades to finish the task, Boguski and his colleagues are refining high-throughput methods that should allow them to complete their atlas by 2006.
The Allen Institute's initiative will show you where all of the genes in the mouse brain are expressed, but if you're interested in gene activity in individual brain cells, your favourite project is likely to be GENSAT — the Gene Expression Nervous System Atlas.
GENSAT's scientists, led by Nat Heintz of Rockefeller University in New York, place each gene under investigation into a bacterial artificial chromosome (BAC), along with a genetic element that stitches a fluorescent tag onto the protein encoded by the gene. By creating transgenic mice that carry these BACs, the researchers can identify — by sight — the cells in which a gene of interest is normally active, and can work out how these cells connect with the rest of the brain. The same BACs can also be used to introduce other genetic modifications into these cells, providing a unique tool to investigate their biology.
GENSAT's first images can already be seen on its website, which was launched in October alongside a paper introducing the project (S. Gong et al. Nature 425, 917–925; 2003). GENSAT scientists aim to study some 300 genes each year, through funding from the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.
This year also saw the launch of the German-led Human Brain Proteome Project, which will catalogue all of the proteins found in the brain. And in the summer, the International Consortium for Brain Mapping, which since 1993 has been compiling a database of structural images of human brains — covering both healthy individuals and patients with neurological or psychiatric disorders — launched itself as a neuroscience resource. Most of the subjects represented in the database have also provided blood samples, which is a boon for researchers who want to investigate the association between particular genetic profiles and unusual brain structures seen in various diseases.
Now that these projects — and related initiatives focusing on particular brain processes or regions — are up and running, perhaps it's time to commission a sequel to the Decade of the Brain.
Allen Brain Atlas → http://www.brainatlas.org
BMAP → http://trans.nih.gov/bmap
GENSAT → http://www.gensat.org
Human Brain Proteome Project → http://www.hbpp.org
International Consortium for Brain Mapping → http://www.loni.ucla.edu/ICBM
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Abbott, A. Genomics on the brain. Nature 426, 757 (2003). https://doi.org/10.1038/426757a