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

描述（由申请人提供）：蜱是强制性的外部寄生虫，以宿主的血液为食，通常传播病原体，包括细菌，原生动物和病毒。蜱传疾病给畜牧业造成了巨大的经济损失，也给人类带来了健康风险。蜱的唾液分泌物通过调节宿主的反应在供血中起着重要的作用。我们建议研究肽能系统，因为它与控制唾液腺有关的黑腿蜱，肩胛骨蜱，这是美国北部最重要的蜱之一，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：肌抑制肽（MIP）和色素分散激素（PDF）。特异性目的1是鉴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，但我们将通过使用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。特异性目的2将进一步表征MIP，这是在初步研究中强烈支持控制唾液腺功能的神经肽。克隆编码MIP及其受体的基因将随后研究其表达模式和功能。本研究将首次描述控制蜱唾液腺的神经肽，并将为下一步研究中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破坏蜱虫唾液功能的化合物和疫苗。该研究结果将对其他对经济和健康产生重大负面影响的蜱类的研究产生重大影响。本研究的结果将有助于了解蜱唾液腺神经控制的基本生物学原理，为研究其他蜱类提供理论依据，并为开发对环境无害的杀螨化合物/策略提供合理途径。这项研究最终有望设计出破坏唾液功能的化合物和疫苗，防止蜱虫传播疾病，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.