"If neurons are to function properly, they need to control with exquisite precision where each protein in their structure is synthesized. When that process is disrupted in the human brain, severe cognitive problems can ensue. Fragile-X mental retardation is an example. Remarkably, we geneticists know a lot about how gene expression is regulated in the nucleus, where DNA is transcribed to RNA. But we know surprisingly little about the spatial regulation of protein synthesis. From the perspective of the cell-body, you have to specify on which 'leaf' of the neuronal tree a protein is being made."
Dubnau notes that the project is significant from the standpoint of basic science; the regulatory mechanism he describes is still unknown. It also promises to shed new light on brain illnesses -- Fragile-X is only one of several -- "in which it has become clear that spatial and temporal control" of the process by which RNAs are translated into brain proteins in some manner goes awry.
"We'll focus at first on Fragile-X as a kind of test case for our approach," Dubnau says. "At the same time, we hope to provide the neuroscience community a library of fruit fly strains that will enable researchers around the world to query the regulation of genes in the nervous system, one by one. If many researchers take this approach, we can envision a collaborative process, akin to what computer scientists call parallel processing, that might open new windows on regulatory anomalies implicated in mental illness."
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory