Neural mechanisms integrating metabolism and reproductive behaviour in Drosophila melanogaster

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The integration of external stimuli with internal physiological states to elicit a behavioural response is a fundamental question in neurobiology. My research program aims to uncover how peripheral signals are collected and interpreted in the CNS to establish copulatory behaviour, how an animal adjusts its feeding behaviour to maintain energy balance in response to reproductive behaviour, and the factors that ensure copulation is maintained in the presence of environment stress before sperm is successfully transferred. Over the next five years of my NSERC Discovery Grant program, my three main objectives will be to: 1) Discover how peripheral mechanosensory neurons control copulatory behaviour 2) Investigate the role of the highly conserved metabolic endocrine factor dNUCB1 in the coordination of feeding and energy metabolism with reproductive behaviour 3) Determine how peripheral mechanosensory input and energy status are linked to the neural circuit that regulates copulation persistence - the maintenance of copulation in the presence of environmental stress We will use a wide range of genetic tools available in the fly community to target gene expression to specific cells to uncover the cellular and molecular function requires to control copulatory behaviour (e.g. duration and posture), dNUCB1 induced changes in feeding behaviour, and how peripheral sensation and internal energy status contribute to copulation persistence. We will express fluorescent proteins and perform immunochemistry with confocal microscopy to visualize cellular morphology. Functional studies will be performed by target expression of genes that perturb cellular functions (e.g. neuronal silencers, activators, genes that promote cell death) or molecular functions (e.g., RNAi that knockdown the expression of specific genes) followed by phenotypic analysis. Readouts for each genetic manipulation will include behavioural assays (courtship and feeding), enzymatic assays and mass spectrometry to quantify energetic molecules in the whole animal. Biochemical and biophysical assays will corroborate the identification of genetic interactors to unravel the underlying molecular mechanisms. This proposal implicates both human and animal health. Discovering how mating posture is controlled by the nervous system may help us understand proprioception, which is impaired in many human and animal neurological disorders. Understanding how the highly conserved endocrine factor dNUCB1 affects energy metabolism may help us tackle the growing problem of obesity in humans and pets. Finally, knowing how the environment interacts with the nervous system to govern copulation persistence could help us understand the potential impact of the environment on species conservation. The fly model allows us to explain these complicated processes at the cellular and molecular level. This level of understanding will allow for the adjustment of any abnormalities that may impact reproductive success.