Neural and hormonal control of visceral systems

我们的长期目标是研究昆虫的细胞、组织和器官系统是如何受到神经元和神经内分泌途径的调节和整合的，这些神经内分泌途径利用各种神经活性化学物质(神经肽和胺)、G蛋白偶联受体(GPCRs)和第二信使。我们感兴趣的是这些系统如何参与成功的行为，包括繁殖、消化、营养和废物的循环以及蜕皮行为。我们观察到，一些神经活性化学物质在各种类型的细胞中表达，因此这些神经活性化学物质本身可能代表相互作用的功能单位，使昆虫转向新的功能状态或行为。此外，这些神经活性化学物质也是脑-肠轴的组成部分，因此在消化道的内分泌/神经系统、神经内分泌系统、中枢神经系统(CNS)以及血淋巴(血液)和神经激素的循环之间起着联系作用。本研究计划的研究目标如下：1)明确生殖结构及相关内脏组织的神经内分泌综合控制。(2)通过神经肽在中枢神经系统和相关的外周系统(心脏、消化系统)上的协调作用，确定对蜕皮行为(外骨骼脱落)的综合控制。我们的科学方法是整体的，从基因到行为都包含了多方面的内容。我们使用包括分子生物学、药理学、神经生理学、生理分析、肽分离、神经图谱和免疫组织化学在内的多种技术来定义用于对这些行为进行综合控制的神经底物和神经回路(包括它们的神经活性化学物质和受体)。新颖性和预期意义：我们的长期目标是研究细胞之间是如何相互沟通的，以便产生适当的生理和行为输出。我们识别和定义在我们的模型系统中使用的各种神经化学物质之间的相互作用，并研究器官系统的相互作用/协调。昆虫研究的重要性越来越多地在于测试和论证神经组织和功能的普遍原理，同时为新的害虫控制策略的目标识别独特的特征。例如，就像制药业一样，由于对当前一代杀虫剂的抗药性不断增强，农用化学工业正在将神经活性化学物质和GPCRs作为新的害虫控制策略的目标。未来是充满希望的，特别是对于神经肽来说，与其使用相关的内在问题已经被克服。这种控制的需要与我们的模式昆虫--游动线虫和多刺线虫--尤其相关。蝗虫是一种农业害虫，它们吞噬或破坏庄稼，影响着地球上20%以上的土地和世界上65个以上最贫穷的国家。它们的蜂拥而至在许多发展中国家造成了毁灭性的后果。这种具有重要医学价值的昆虫是人类恰加斯病的媒介，虽然一度被认为仅限于美洲，但由于人类迁徙和输血，恰加斯病现在在世界各地都有发生。例如，据估计，美国有30万人感染，西班牙有5万人，加拿大有2000人。因此，如上所述，这项研究有可能发现未来可以开发成生物农药的先导化合物。

Our long-term goals are to study how cells, tissues and organ systems in insects are regulated and integrated by neurons and neuroendocrine pathways that utilize a variety of neuroactive chemicals (neuropeptides and amines), G-protein coupled receptors (GPCRs) and second messengers. We are interested in how these systems participate in successful behaviours; including aspects of reproduction, digestion, circulation of nutrients and waste, and ecdysis behaviour. We have observed that some neuroactive chemicals are expressed in a variety of cell types and so it is possible that these neuroactive chemicals might in themselves represent functional units that interact to bias the insect towards a new functional state or behaviour. In addition, these neuroactive chemicals are also components of the brain-gut axis, and therefore serve as a link between the endocrine / neural system of the digestive tract, the neuroendocrine system, the central nervous system (CNS), and circulation of haemolymph (blood) and neurohormones. The research objects of the proposed research program lie in the following areas: 1) to define the integrative neuroendocrine control of reproductive structures and associated visceral tissues (eg. digestive, cardiac) in the agricultural pest Locusta migratoria and in the medically-important vector of Chagas’ disease, Rhodnius prolixus; and 2) to define the integrative control of ecdysis behaviour (shedding of the exoskeleton) through the coordinated action of neuropeptides on CNS and associated peripheral systems (cardiac, digestive, skeletal muscle). Our scientific approach is holistic and incorporates multi-facetted aspects from gene to behaviour. We define the neural substrates and circuits (including their neuroactive chemicals and receptors) used in the integrative control of these behaviours using a variety of techniques including molecular biology, pharmacology, neurophysiology, physiological assays, peptide isolation, neural mapping, and immunohistochemistry. Novelty and expected significance: Our long term goal is to study how cells communicate with one another in order to produce an appropriate physiological and behavioral output. We identify and define the interactions between the diverse neurochemicals which are used in our model systems, and also look at interactions / coordination of organ systems. The importance of research into insects lies increasingly in the testing and demonstration of universal principles of neural organization and functioning, while identifying unique features for target of novel pest control strategies. For example, just like the pharmaceutical industry, the agrochemical industry is targeting neuroactive chemicals and GPCRs for novel pest control strategies due to the ever increasing resistance to the current generation of pesticides. The future is hopeful, especially for neuropeptides, where the intrinsic problems associated with their use have been overcome. This need for control is particularly relevant for our model insects, L. migratoria and R. prolixus. Locusts are agricultural pests, eating or destroying crops and affecting over 20% of the earth’s land and more than 65 of the world’s poorest countries. Their swarms lead to devastating consequences in many developing countries. The medically-important insect, R. prolixus, is the vector of human Chagas disease, and whilst once considered to be confined to the Americas, Chagas disease now occurs throughout the World due to human migration and blood transfusions. For example, it is estimated that 300,000 people are infected in the USA, 50,000 in Spain and 2,000 in Canada. Therefore, this research, as outlined above, has the potential to discover lead compounds that can be developed into bio-pesticides in the future.