Take
the most complex organ in the human body, superimpose the legacy of
biology’s biggest research project, and what have you got? An
unprecedented brain map that is set to transform studies of
neuroscience and brain disease.

The Allen Institute for Brain Science
in Seattle, Washington, US, is today launching a four-year, $55-million
effort to build a three-dimensional map documenting the levels of
activity of some 20,000 different genes across the human brain.

“The
Human Genome Project was the ‘what’, and our project is the ‘where’,”
says Allan Jones, the institute’s chief scientific officer.

Established
in 2003 with a $100-million gift from Microsoft co-founder Paul Allen,
the Allen institute has already created a similar atlas of the mouse brain, unveiled in December 2006.

By
revealing patterns of gene activity, the mouse atlas has allowed
neuroscientists to identify functionally important regions that were
invisible simply by looking at the brain’s anatomy.

Evolution insights

“That’s
why the brain is such a unique structure,” says Greg Foltz, a
neurosurgeon at the Swedish Neuroscience Institute, also in Seattle.
“Its function is very much embedded in its anatomy.”

Foltz’s team has also used the mouse atlas to help home in on two genes, known as BEX1 and BEX2, which seem to be silenced in a form of brain cancer called glioma.
An atlas of the human brain should be an even more powerful tool in
identifying what goes wrong at the gene level in cancer and other
diseases, he says.

For
instance, some neuroscientists suspect that autism may be linked to
abnormalities in a paired structure called the amygdala, involved in
processing emotional information. This can be tested by comparing
patterns of gene activity in autistic people with that in the atlas,
which will be drawn up by studying the brains of recently deceased
healthy people.

Comparisons
between the mouse and human brain atlases should also yield insights
into the evolution of our advanced cognitive abilities, suggests David Anderson, a neuroscientist at the California Institute of Technology
in Pasadena, and one of the Allen institute’s scientific advisers. “Are
there fundamental differences in the organisation of the brain?” he
asks.

Huge task

The mouse atlas was produced using a method called “in situ hybridisation”, in which thin slices of brain tissue are bathed in a solution containing molecular probes that bind to messenger RNA sequences produced by each gene. This gives a very detailed map of gene activity, down to the level of individual cells.

Trying
to repeat this effort for all 20,000 genes across an organ about 2000
times larger than the mouse brain is impractical, for now. So Allen
institute scientists will instead divide the human brain into between
500 and 2000 anatomical regions, and study gene activity in each by
washing extracts from tissues in these regions across “gene chips” that
can record which messenger RNA is present.

Once
results from this initial phase of the project are in, which will take
about two years, the institute’s scientists will perform in situ
hybridisation across the whole brain for up to 500 genes with the most
interesting patterns of activity.