Neural mechanisms integrating metabolism and reproductive behaviour in Drosophila melanogaster

将外部刺激与内部生理状态相结合以引发行为反应是神经生物学中的一个基本问题。我的研究项目旨在揭示外周信号如何在中枢神经系统中收集和解释以建立交配行为，动物如何调整其摄食行为以维持能量平衡以响应生殖行为，以及在精子成功转移之前确保在环境压力存在的情况下维持交配的因素。在我未来五年的国家科学研究委员会发现基金项目中，我的三个主要目标是：1)发现外周机械感觉神经元如何控制交配行为2)研究高度保守的代谢内分泌因子dNUCB1在摄食和能量代谢与生殖行为协调中的作用3)确定外周机械感觉输入和能量状态如何与调节交配持久性的神经回路联系在一起-在环境压力存在下维持交配dNUCB1诱导的摄食行为的改变，以及外周感觉和内部能量状态如何促进交配持续。我们将表达荧光蛋白，并使用共聚焦显微镜进行免疫化学观察细胞形态。功能研究将通过干扰细胞功能的基因（如神经元沉默者、激活者、促进细胞死亡的基因）或分子功能（如敲低特定基因表达的RNAi）的靶表达进行，然后进行表型分析。每次基因操作的读数将包括行为分析（求偶和喂养），酶分析和质谱分析，以量化整个动物的高能分子。生化和生物物理分析将证实遗传相互作用的鉴定，以揭示潜在的分子机制。这一建议涉及人类和动物的健康。发现交配姿势是如何由神经系统控制的，可能有助于我们理解本体感觉，它在许多人类和动物的神经系统疾病中受损。了解高度保守的内分泌因子dNUCB1如何影响能量代谢，可能有助于我们解决人类和宠物日益严重的肥胖问题。最后，了解环境如何与神经系统相互作用以控制交配持久性可以帮助我们了解环境对物种保护的潜在影响。果蝇模型使我们能够在细胞和分子水平上解释这些复杂的过程。这种程度的理解将允许调整任何可能影响生殖成功的异常。

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.