Modeling the genetic basis for human sleep disorders in Drosophila

Sleep research in Drosophila is not only here to stay, but is making impressive strides towards helping us understand the biological basis for and the purpose of sleep—perhaps one of the most complex and enigmatic of behaviors. Thanks to over a decade of sleep-related studies in flies, more molecular methods are being applied than ever before towards understanding the genetic basis of sleep disorders. The advent of high-throughput technologies that can rapidly interrogate whole genomes, epigenomes and proteomes, has also revolutionized our ability to detect genetic variants that might be causal for a number of sleep disorders. In the coming years, mutational studies in model organisms such as Drosophila will need to be functionally connected to information being generated from these whole-genome approaches in humans. This will necessitate the development of appropriate methods for interpolating data and increased analytical power to synthesize useful network(s) of sleep regulatory pathways—including appropriate discriminatory and predictive capabilities. Ultimately, such networks will also need to be interpreted in the context of fundamental neurobiological substrates for sleep in any given species. In this review, we highlight some emerging approaches, such as network analysis and mathematical modeling of sleep distributions, which can be applied to contemporary sleep research as a first step to achieving these aims. These methodologies should favorably impact not only a mechanistic understanding of sleep, but also future pharmacological intervention strategies to manage and treat sleep disorders in humans.