Investigating Molecular Assembly and Dynamics of Tick Cement proteins

研究蜱水泥蛋白的分子组装和动力学

• 批准号: 9304705
• 负责人: SARAH E MORGAN
• 金额: $ 44.4万
• 依托单位: UNIVERSITY OF SOUTHERN MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9304705
• 关键词: Adhesives; Amblyomma; Animals; Anticoagulants; Antifreeze; Applications Grants; Artificial Membranes; Biochemical; Biocompatible Materials; Biological; Biological Assay; Biological Process; Biomechanics; Blood; Cell Proliferation; Cells; Characteristics; Climate; Co-Immunoprecipitations; Collaborations; Collection; Communicable Diseases; Cone; Data; Dermacentor; Dermal; Dermis; Development; Electron Microscopy; Environment; Family; GRP gene; Gene Expression; Genes; Glycine; Health; Hemostatic Agents; Heterogeneity; Hour; Human; Immune response; Inflammatory Response; Injection of therapeutic agent; Insect Proteins; Interruption; Knowledge; Methods; Microbe; Monoclonal Antibodies; Morphology; Oral cavity; Organism; Pain; Pathogenesis; Pathogenicity; Phase; Physiological Processes; Plants; Play; Positioning Attribute; Post-Translational Protein Processing; Prevention; Process; Property; Protein Family; Proteins; Proteomics; Pruritus; Public Health; Quantitative Reverse Transcriptase PCR; RNA Interference; Reagent; Recombinant Proteins; Recombinants; Research; Role; Saliva; Salivary; Salivary Glands; Secure; Skin; Stress; Structural Protein; System; Techniques; Temperature; Testing; Ticks; Time; Transcript; Up-Regulation; Vascular blood supply; Vector-transmitted infectious disease; antimicrobial; biomaterial compatibility; design; experimental study; fascinate; feeding; genetic approach; immunoregulation; innovation; insight; mechanical properties; molecular assembly/self assembly; molecular dynamics; multidisciplinary; nanomechanical; nanomechanics; novel; pathogen; prevent; protein expression; reverse genetics; scaffold; student training; tool; transcriptome sequencing

Summary Ticks must use their barbed mouthparts (hypostome) to pierce deeply into the host’s dermis (skin), then encase the hypostome in a cement cone in order to maintain a firm, pain and itch- free attachment, subsequently transmitting infectious disease agents into the victim. Two types of cement have been found in ticks; early cement which is secreted only minutes after attachment and hardens rapidly, and late cement which is secreted 24 hours after attachment to the host and hardens gradually. These secreted cement cones are composed of several glycine-rich proteins (GRPs) which are a large family of diverse proteins that are known for their adhesive and tensile characteristics. Such properties may play an important role in host skin attachment to gain an uninterrupted supply of blood over a prolonged period of time. Our long- term plan in the AREA grant application is to reveal the functions and biochemical properties of novel GRPs in cement cone assembly, stealth attachment, hematophagy (blood feeding) and climatic adaptation. We will test our central hypothesis that biochemical and biomechanical properties of GRPs assist in the undetected attachment to the host, providing access to an uninterrupted supply of blood by serving as scaffolding for the cement cone apparatus. Our multidisciplinary team will test the hypothesis using a combination of artificial membrane feeding, structural, proteomics, and reverse genetics approaches. Specific aims are to: 1) determine the role of unique salivary GRPs in cement cone assembly and secure attachment by using an artificial membrane feeding system, and 2) define the biochemical properties of uncharacterized recombinantly expressed cement cone proteins. Targeting tick cement proteins may provide an innovative way to create a hostile situation for tick attachment, and ultimately interrupt the inoculation of tick-borne pathogens into the host. Understanding the mechanisms of cement assembly that allow the tick to secure a stable, stealthy attachment will provide insight into developing new control and prevention methods.

概括 蜱必须使用带刺的口器（下体）深深刺入宿主的真皮 （皮肤），然后将下口包裹在水泥锥中，以保持牢固、疼痛和瘙痒- 自由附着，随后将传染病病原体传播给受害者 两种类型。 在早期的蜱虫中发现了水泥，这种水泥在几分钟后才分泌出来； 附着并迅速硬化，附着后24小时分泌出晚期骨水泥 这些分泌的水泥锥体由几个组成。 富含甘氨酸的蛋白质（GRP）是一个由多种蛋白质组成的大家族，以其 这些特性可能在宿主皮肤中发挥重要作用。 我们长期致力于获得不间断的血液供应。 AREA 拨款申请中的长期计划是揭示以下物质的功能和生化特性 新型 GRP 用于水泥锥体组装、隐形附件、噬血（吸血）和 我们将测试我们的中心假设，即生物化学和生物力学。 GRP 的属性有助于未检测到地连接到主机，从而提供对主机的访问 通过充当水泥锥装置的脚手架，不间断地供应血液。 多学科团队将结合使用人工膜喂养来测试这一假设， 结构、蛋白质组学和反向遗传学方法的具体目标是：1) 确定 独特的唾液 GRP 在水泥锥组装和安全附着中的作用 人工膜饲喂系统，2) 定义未表征的生化特性 重组表达的粘固锥蛋白可以提供一种靶向蜱粘固蛋白的方法。 创新的方式为蜱虫附着创造一个敌对的环境，并最终中断蜱虫的附着 了解水泥将蜱传病原体接种到宿主体内的机制。 允许蜱虫固定一个稳定、隐秘的附件的组件将提供洞察力 开发新的控制和预防方法。