Evaluating starvation resistance in Drosophila melanogaster

Feeding is a complex behaviour that must be regulated to maintain an appropriate energy balance and avoid death by starvation. Adjustments to either the homeostatic regulation, including complex signaling cascades and neuropeptides, or to the post-feeding reward systems could substantially affect the reserve of energy and thus survivorship in times of nutrient adversity. This thesis uses Drosophila melanogaster to model the biological basis of starvation and determine how to enhance survivorship upon amino acid starvation media via manipulating components that control feeding. The conserved insulin receptor pathway and its endpoint effector the foxo transcription factor are pivotal for survival during nutritional stress. The Akt1 kinase and the Sir2 deacetylase are modifiers of foxo activity. Novel Akt1 hypomorphs show a significant increase in survival on amino acid deprived media, yet have decreased lifespan and growth when aged upon standard media. When these mutants are combined with null foxo mutants, biometric analysis and longevity evaluation indicate a phenotype similar to the original foxo mutant signifying its necessity in the Akt1 phenotype. Investigation of mutant Sir2 heterozygotes showed that they do not have altered growth when raised upon standard conditions, yet exhibit a greatly extended lifespan when reared on both a standard diet and when starved of amino acids. The neuropeptide NPF, a homologue of mammalian NPY, acts to induce feeding within the homeostatic regulation of the behaviour. Drosophila also bear a shorter form of NPF known as short NPF (sNPF) that can influence feeding. Overexpression or reduced expression of NPF or sNPF increased sensitivity and diminished survivorship upon amino acid starvation media. The neural hormone regulator, the dopamine transporter (DAT) works to clear dopamine from the synapses. This action may manipulate the post-feeding reward circuit in that lowered dopamine levels depress feeding and excess dopamine can encourage feeding. When DAT is either over-expressed or reduced via mutation, Drosophila have an increased sensitivity to amino acid starvation. Taken together these results indicate that subtle variations in the expression of key components of these systems impacts survivorship during reduced nutrient conditions. These findings may advance the understanding of the biological response to starvation to aid in treatment of eating disorders or malnourishment.