Neuroendocrine systems regulating physiological processes in blood-feeding arthropods

神经内分泌系统调节食血节肢动物的生理过程

• 批准号: RGPIN-2014-06681
• 负责人: Paluzzi, JeanPaul
• 金额: $ 2.11万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=589155
• 关键词: Neuroendocrine; systems; regulating; physiological; processes

My research program focuses on the biology of blood-feeding arthropods. I examine the mechanisms by which signaling molecules, called neurohormones, are released from the central nervous system and control numerous physiological processes by regulating the activity of tissues in the visceral system including the gastrointestinal tract and reproductive tissues. My research aims to discover and characterize regulatory systems involving hormones and other neurochemicals that control many physiological and behavioral processes related to feeding, digestion, metabolism, excretion, hydromineral balance, reproduction, growth and development in blood-feeding arthropods including ticks (Ixodes scapularis) and mosquitoes (Aedes aegypti). Neuroendocrine systems will be investigated at the molecular, cellular and tissue level in order to determine their importance and contribution to the biology of these organisms. By examining these systems at multiple levels of complexity, the details are more readily realized and we can then integrate this knowledge of individual signalling components to the whole organism. With the identification of tissue targets regulated by hormonal factors, we will use various assessment methods to determine the roles of these neuroendocrine systems in mosquitoes and ticks. For example, targets of primary interest include the tissues of the alimentary canal (i.e. gut), which play roles in digestion and assimilation of ingested materials, elimination of toxins (including pesticides), immune response and are also chiefly involved in the maintenance of salt and water balance. Similarly, other neurochemicals acting as neurohormones regulate processes related to development and reproduction. We undertake a multi-disciplinary approach to characterize these neuroendocrine regulatory systems utilizing techniques that span the realms of physiology, endocrinology and molecular biology to uncover roles and functions. In addition, in order to comprehensively understand these neuroendocrine signaling networks, which include the hormones and their receptor proteins that are expressed in target cells and tissues, we utilize cell-culture based techniques to validate ligand (i.e. the hormone) and receptor (i.e. the cellular target and cellular elicitor) coupling. In this way, we confirm functional interaction, binding specificity and can elucidate intracellular signalling pathways and mechanisms of action. Some of the fundamental questions driving our research on mosquitoes and ticks include: What neurohormones govern ionic and osmotic balance in these blood-feeding human disease vectors? Which hormones control reproductive behavior and related physiological processes? Do similar signalling molecules control common activities in diverse blood-feeding arthropod species? Once the neurochemicals are elucidated, we seek to identify how target cells and tissues interpret the information carried in the form of a chemical message, which ultimately culminates in a physiological response leading to behavior. The information gained from this research can provide fundamental insights for development of lead compounds useful for control or eradication of these disease vectors. More specifically, integrating the knowledge gained on the biology of these blood-feeding arthropods with data obtained from testing of novel compounds capable of interfering with endogenous neuroendocrine signaling networks, may lead to improved vector control strategies in the future. The proposed research will provide fundamental insight into the basic biology of these organisms and further our knowledge on these medically-important species that have adapted to gorging on vertebrate blood and act as chief vectors of various human and animal diseases.

我的研究方向是吸血节肢动物的生物学。我研究从中枢神经系统释放的被称为神经激素的信号分子的机制，并通过调节包括胃肠道和生殖组织在内的内脏系统组织的活动来控制许多生理过程。我的研究旨在发现和表征涉及激素和其他神经化学物质的调节系统，这些系统控制着与吸血节肢动物（包括蜱（肩胛骨伊蚊）和蚊子（埃及伊蚊））有关的许多生理和行为过程，包括进食、消化、代谢、排泄、水矿物质平衡、繁殖、生长和发育。神经内分泌系统将在分子、细胞和组织水平上进行研究，以确定它们对这些生物体的生物学的重要性和贡献。通过在多个复杂层次上检查这些系统，我们可以更容易地了解细节，然后我们可以将单个信号组件的知识整合到整个生物体中。在确定受激素因素调控的组织靶点后，我们将使用各种评估方法来确定这些神经内分泌系统在蚊子和蜱虫中的作用。例如，主要关注的目标包括消化道（即肠道）的组织，它们在消化和吸收摄入的物质、消除毒素（包括杀虫剂）、免疫反应中发挥作用，并主要参与维持盐和水的平衡。同样，其他神经化学物质作为神经激素调节与发育和繁殖有关的过程。我们采用多学科的方法来表征这些神经内分泌调节系统，利用跨越生理学，内分泌学和分子生物学领域的技术来揭示其作用和功能。此外，为了全面了解这些神经内分泌信号网络，包括在靶细胞和组织中表达的激素及其受体蛋白，我们利用基于细胞培养的技术来验证配体（即激素）和受体（即细胞靶标和细胞激发子）的偶联。通过这种方式，我们确认了功能相互作用，结合特异性，并可以阐明细胞内信号通路和作用机制。推动我们对蚊子和蜱虫进行研究的一些基本问题包括：在这些供血的人类疾病载体中，是什么神经激素控制着离子和渗透平衡？哪些激素控制生殖行为和相关生理过程？在不同的吸血节肢动物物种中，类似的信号分子是否控制着共同的活动？一旦神经化学物质被阐明，我们试图确定目标细胞和组织如何解释以化学信息形式携带的信息，这些信息最终在导致行为的生理反应中达到高潮。从这项研究中获得的信息可以为开发用于控制或根除这些病媒的先导化合物提供基本见解。更具体地说，将这些吸血节肢动物的生物学知识与能够干扰内源性神经内分泌信号网络的新型化合物的测试数据相结合，可能会在未来改善媒介控制策略。拟议的研究将为这些生物的基本生物学提供基本的见解，并进一步了解这些医学上重要的物种，这些物种已经适应了吞食脊椎动物的血液，并成为各种人类和动物疾病的主要载体。