Molecular profiling of antipsychotic drug function
- Elizabeth A. Thomas
- Molecular Neurobiology
Where we started In the present era of the nearing completion of the nucleotide sequences of the human genome and of several model organisms, it is easy to overlook the common viewpoint of 20 years ago, especially among neuroscientists. It was clear at that time intellectually that the genome encoded the protein set and that the proteins provided the hardware for the biochemical operation of the organism. Nevertheless, it was not widely evident that one would be able to determine the protein set via nucleic acid analyses in the relatively near term. In part, this belief was attributable to the vastness of the genome, the then-recently discovered fact that most protein-coding regions in the genome are interrupted by noncoding introns, and the lack of sufficient computing power to store and analyze the information. But it was also attributable to a generally held antipathy toward descriptionbased studies: one cloned and sequenced genes whose protein products had been found already, either through biochemical or genetic studies, to be functionally interesting. Descriptive studies of the sort that are presently classified under the rubric of “genomics” were unfashionable (cf. Barnstable et al., 1983). It was also not clear that even if one had the protein set as a list of putative amino acid sequences that this would give one much of a running start for understanding how any organ functioned, especially one as complex as the brain. The finding that a large percentage of proteins fall into families that share structures and biochemical activities has given instant meaning to many newly determined amino acid sequences. The advent of methods to produce synthetic and recombinant proteins to serve as biochemical and immunological reagents has greatly aided in the functional characterization of these newly discovered proteins, as have methods to manipulate their genes in experimental animals so as to alter their expression and activity in vivo. This article intends to show how conceptual and technological advances in molecular biology have moved neuroscience into the postgenomic era.