Neural mechanisms integrating metabolism and reproductive behaviour in Drosophila melanogaster

将外部刺激与内部生理状态整合以引起行为反应是神经生物学中的一个基本问题。我的研究计划旨在揭示如何在中枢神经系统中收集和解释外周信号以建立交配行为，动物如何调整其进食行为以维持能量平衡以应对生殖行为，以及确保在精子成功转移之前在环境压力下维持交配的因素。 在接下来的五年里，我的NSERC发现资助计划，我的三个主要目标将是：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dNUCB 1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续性的神经回路联系在一起-在环境压力下维持交配我们将使用果蝇群落中广泛的遗传工具，将基因表达靶向特定细胞，以揭示细胞和分子功能。需要控制交配行为（例如持续时间和姿势）、dNUCB 1诱导的进食行为变化，以及外周感觉和内部能量状态如何影响交配持续性。我们将表达荧光蛋白，并进行免疫化学共聚焦显微镜观察细胞形态。功能研究将通过干扰细胞功能（例如神经元沉默剂、激活剂、促进细胞死亡的基因）或分子功能（例如，敲低特定基因表达的RNAi），然后进行表型分析。每个基因操作的读数将包括行为测定（求偶和进食）、酶测定和质谱分析，以量化整个动物中的能量分子。生物化学和生物物理分析将证实遗传相互作用的识别，以解开潜在的分子机制。 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受，这在许多人类和动物的神经系统疾病中都是受损的。了解高度保守的内分泌因子dNUCB 1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续性可以帮助我们了解环境对物种保护的潜在影响。苍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。这种理解水平将允许调整可能影响生殖成功的任何异常。

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.