Tool to study brain development leads to new drugs
brain development, which will help scientists discover the genetic
origins of brain cancers, which could speed development of novel
drugs to treat them.
The tool, called the mouse Brain Gene Expression Map (BGEM), will identify brain disorders, such as tumours and some psychiatric diseases, which are caused by gene mutations that arise during development of this organ.
The scientists from St. Jude Children's Research Hospital have given investigators around the world free access to this Internet-based tool, in the hope that uptake will be quick and varied.
The continual updating and completion of the BGEM Web site will be crucial to scientists. More than half of the approximately 25,000 genes in the mouse are thought to be involved in the development and function of the nervous system, but scientists have determined the function of only 30 per cent of them.
"The similarity of the mouse and human brain make this map useful to researchers who study the development of the human brain and the origin of brain tumours from gene mutations," said Tom Curran, co-chair of Developmental Neurobiology at St. Jude.
"The BGEM represents a new strategy for exchanging information among researchers that will accelerate our understanding of the human nervous system," he added.
The tool takes drug development one step closer to a stage where researchers will be able to do certain studies to confirm hypotheses using a computer interface that links data to many other kinds of gene information, without the need to go into a laboratory setting.
The BGEM is a growing, encyclopaedic collection of tens of thousands of images as seen through a microscope. The images are obtained at distinct time points and show where and when specific genes are expressed at each of four developmental stages.
Gene expression refers to the production of mRNA, which becomes the blueprint the cell uses to make the protein coded for by that gene. It is visible because special tags called probes bind to messenger RNA (mRNA) - the decoded form of the gene - and release a signal that can be seen using a special microscope.
The BGEM links these images with the most up-to-date information on those genes, such as their function, location on chromosomes and exact DNA sequence. The BGEM gathers this information through direct links to the scientific databases PubMed, LocusLink, Unigene and the Gene Ontology Consortium, which is housed at the National Center for Biotechnology Information in the National Library of Medicine.
In turn, the BGEM images are used by the Gene Expression Nervous System Atlas (GENSAT), which seeks to document the expression of all genes in the nervous system.
"A researcher who discovers a previously unrecognised gene that is expressed during brain development can rapidly determine how it fits into the overall scheme of brain development," said Craig Brumwell, the GENSAT manager in St. Jude Developmental Neurobiology.
"The BGEM helps researchers skip over much of the drudgery of digging up information from the literature or from other databases."
The BGEM already contains detailed information and images of the expression of hundreds of genes that play key roles directing brain development, controlling the expression of other genes, guiding protein production and transporting molecules within the cell.
A key part of the BGEM's success was the development at St. Jude of bioinformatics software that routinely searches scientific databases for new information on genes linked to brain development, said Perdeep Mehta, the group leader in bioinformatics at St. Jude's Hartwell Center for Bioinformatics and Biotechnology.
"Our ability to link images of gene expression patterns to information on those genes in other databases increases the value of each new gene discovery," Mehta said.
A report on the development and availability of the BGEM appears in the March 28 issue of >PLoS Biology.
