Dr. Cassill’s lab is interested in the mechanism of signal transduction in the Drosophila visual system. They are specifically pursuing two areas, that of attenuation of signal response and retinal degeneration caused by mutation of members of the signal pathway. There are two projects in the first area - the isolation of retina-specific serine/theonine protein kinases and characterization of a mutant line which appears to be defective in signal attenuation. The lab has synthesized two degenerate oligonucleotides which encode conserved domains in protein kinases and used these with PCR to amplify kinases from a library of Drosophila retinal cDNAs. Thus far, the lab has isolated 21 novel kinases and are characterizing these as well as screening for additional kinases. They are also characterizing a mutant Drosophila isolated from an enhancer trap screen which has a phenotype of responding with twice the normal level of activity to light pulses. They have isolated the genomic region containing the mutation and are characterizing the transcripts in this region to identify the affected gene.
Mutations in the visual cascade can lead to retinal degeneration. The lab has screened 70,000 flies and isolated 14 mutants which undergo dominant retinal degeneration. Thirteen of these mutations are in the light receptor rhodopsin. Interestingly, four of these are the same as mutations occurring in human rhodopsin which cause the disease retinitis pigmentosa (RP). The last mutation does not map to any known members of the visual cascade and may represent a new member of the path. The lab is currently screening for additional mutants, creating mutations in Drosophila rhodopsin which correspond to other human RP mutations, and attempting to isolate the gene responsible for the degeneration in our non-rhodopsin mutant.