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.
“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.
The sheer size of the human brain will make the new project a much bigger challenge.
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.
As well as launching the human brain atlas, the Allen institute is starting two further projects. The first, costing around $15 million over the next two years, will look at the activity of around 4000 mouse genes at different stages in embryological and juvenile development.
A second project, taking about a year to complete at a cost of $2 million, will make an atlas of gene activity in the mouse spinal cord.