Neurpeptidergic control of the salivary gland in the black-legged tick, Ixodes sc

描述(申请人提供)：扁虱是必须的外部寄生虫，以宿主的血液为食，经常传播包括细菌、原生动物和病毒在内的病原体。壁虱传播的疾病给畜牧业造成了巨大的经济损失，也给人类的健康带来了风险。扁虱的唾液分泌物通过调节宿主的反应，在血液摄取中发挥重要作用。我们建议研究黑腿硬蜱的肽能系统，因为它与唾液腺的控制有关，这是美国北部最重要的硬蜱之一，对人类健康构成威胁。我们的初步研究表明，至少有两个肽能系统参与唾液腺的神经控制：推测是肌肉抑制肽(MIP)和色素分散激素(PDF)。具体目的1是确定与唾液功能相关的候选神经肽。虽然我们已经在初步研究中确定了候选神经肽，但我们将通过更全面和组合的方法、蛋白质组学、生物信息学和免疫组织化学来扩大调查范围。特定目的2将进一步表征MIP，这是一种在初步研究中被强烈支持的控制唾液腺功能的神经肽。克隆编码MIP及其受体的基因之后，将研究它们的表达模式和功能。这项研究将首次描述控制扁虱唾液腺的神经肽，并将为下一阶段研究多肽能系统在唾液分泌中的作用提供基础。从这项研究中获得的基本知识有望导致设计出扰乱扁虱唾液功能的化合物和疫苗。拟议的研究结果将对对经济和健康有很大负面影响的其他扁虱物种的研究产生很大影响。与公众健康的相关性拟议工作的结果将有助于人们了解壁虱唾液腺神经控制的基本生物学，这将为研究其他种类的壁虱提供原则，并为开发环境无害的杀螨剂/策略提供合理的方法。这项研究有望最终导致化合物和疫苗的设计，以扰乱唾液功能，防止扁虱传播疾病，最终改善人类健康。

DESCRIPTION (provided by applicant): Ticks are obligatory external parasites that feed on the blood of hosts, and often transmit pathogens, including bacteria, protozoa, and viruses. Tick-borne diseases cause huge economic losses in the animal industry as well as health risks to humans. The salivary secretions of the ticks play an important role in blood feeding by modulating the host response. We propose to investigate the peptidergic system as it relates to control of the salivary gland in the black-legged tick, Ixodes scapularis, which is one of the most important ticks in the northern U.S. as a risk to human heath. Our preliminary study suggests that at least two peptidergic systems are involved in neural control of the salivary gland: putatively, myoinhibitory peptide (MIP) and pigment dispersing hormone (PDF). Specific Aim 1 is to identify candidate neuropeptides relevant to salivary functions. While we already identified candidate neuropeptides in our preliminary study, we will expand the survey by using more comprehensive and combinatorial approaches, proteomics, bioinformatics and immunohistochemistry. Specific Aim 2 will further characterize the MIP which is the neuropeptide strongly supported for the function controlling the salivary glands in the preliminary studies. Cloning of the genes encoding MIP and its receptor will be followed by investigation of their expression patterns and function. This study will provide the first description of neuropeptides controlling the tick salivary gland and will provide a foundation for investigations into the roles of the peptidergic systems in salivary secretion in the next tier of study. The fundamental knowledge obtained from this research is expected to lead to the design of compounds and vaccines that disrupt the tick salivary function. The outcome of the proposed research will have high impacts on the studies in other tick species that have large negative impacts on the economy and health. PUBLIC HEALTH RELEVANCE The outcome of the proposed work will provide an understanding of the basic biology of neural control of the tick salivary gland, which will provide the principles for studying other species of tick, and provide rational approaches to develop environmentally benign acaricidal compounds/strategies. This research is eventually expected to lead to the design of compounds and vaccines to disrupt the salivary functions and to prevent disease transmissions by ticks, ultimately improving human health.