The long term objective of this research is to elucidate mechanisms of visual excitation.
The specific aim of this project is to analyze, on the DNA and RNA levels, a newly isolated Drosophila gene which, when mutant, affects visual transduction. The methodology used to achieve this goal will be molecular genetics, with complementary biochemical, immunological and electrophysiological techniques. Analysis of this gene is expected to provide important information about photoreceptor function. In addition, the techniques used are some of the most powerful ones currently available; similar techniques may be used for the diagnosis and, ultimately, for the treatment of certain disorders of the visual system. According to a current model of visual transduction, the receptor potential of an invertebrate photoreceptor is generated by the superimposition of discrete events known as """"""""bumps."""""""" Each bump is produced by the absorption of a single photon and this bump is a membrane voltage change caused by an increased membrane conductance to sodium ions. With increasing light intensity, the rate of occurrence of the bumps becomes higher and the bumps become smaller (adapt) to result in the increasingly smoother receptor potential. In the mutant transient receptor potential (trp), the receptor potential decays to near baseline during an intense, prolonged stimulus. It seems that in this mutant, unlike in the wild type, the rate of bump occurrence does not increase proportionally with light intensity. Therefore, the defective trp gene appears to affect, selectively, the mechanisms associated with the rate of bump occurrence. The trp mutation has been localized to a region of about 60 kilobasepairs of DNA on the third chromosome. This region of DNA, which includes the trp gene, has been cloned as a set of partially overlapping genomic DNA fragments that spans the region. This stretch of DNA is found to contain genes that encode for four RNA species; two of these RNA species are missing in the trp mutant. This observation suggests that the molecular basis of the mutant phenotype may be due to the lack of a protein(s) encoded by these RNAs. By inference, this protein(s) must be important for normal bump occurrence and, hence, for visual transduction. Since the trp gene is now available, the identity of the gene products can be determined and their roles in visual transduction can be studied in molecular detail.
