Genetic and molecular analysis of multiple functions of the Drosophila melanogaster foraging gene

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We are interested in understanding how genes interact with the environment to generate individual differences in complex traits. Our research focuses on food-related traits including food search, food intake and triglyceride levels in well-fed and food-deprived environments. We use the fruit fly Drosophila melanogaster model with its unsurpassed genetic tool kit, focussing our efforts on the Drosophila foraging gene. The foraging gene gives rise to two natural variants that we call rover and sitter. Rover flies move more, feed less and have lower triglyceride levels than do sitter flies. It is not known how foraging, which encodes a cGMP dependent protein kinase (PKG) accomplishes its multiple functions to affect individual differences in food-related traits. We recently discovered that foraging is a complex 35 kb gene with 12 exons, 4 transcription start sites (minimal promoters) and 1 transcription termination site. It produces many gene products including 21 transcripts representing 9 open reading frames. foraging is found in multiple tissue and cell types throughout development and adulthood. We hypothesize that the gene’s structure and complexity facilitates its many functions. Additionally, we speculate that a given foraging gene product might be used in multiple ways (within the same or different tissues) to affect foraging’s multiple functions. Our specific research questions are: 1) What roles do foraging’s minimal promoters, multiple transcripts and protein isoforms play in food-related traits? 2) Which DNA sequences regulate foraging’s gene products (guiding them regarding when and where to be expressed in the organism) and how does this expression regulate foraging’s food-related traits? 3) What are the underlying molecular mechanisms for the tissue-specific functions of foraging? 4) Which rover and sitter DNA sequence variations segregate with each of the food-related traits? The molecular dissection of the relationships involving genotype, phenotype and the environment is critical for our understanding of individual differences and how they arise. Because foraging's role in food-related traits is conserved in both invertebrates and vertebrates, we will have the ability to generalise our results to other species. From an applied perspective, this new understanding of the relationship between genotype and phenotype is critical for targeted genetic or chemical manipulations. These techniques are commonly used for insect pest management and conservation. Utilizing these applied endeavours will minimize what are thought to be the "side-effects" of these manipulations and understanding the role of the multiple phenotypes affected by relevant major genes and processes holds the key to unlocking the door.