Tick gene expression- in the context of Lyme disease

蜱基因表达——在莱姆病的背景下

• 批准号: 6712064
• 负责人: SUKANYA NARASIMHAN
• 金额: $ 23.89万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6712064
• 关键词: Borrelia; Ixodes; Lyme disease; RNA interference; bacteria infection mechanism; bacterial proteins; complementary DNA; double stranded RNA; fluorescence microscopy; gene expression; gene induction /repression; host organism interaction; laboratory mouse; microarray technology; polymerase chain reaction; salivary glands; ticks; two dimensional gel electrophoresis

DESCRIPTION (provided by the applicant): This R21 proposal builds upon the observations made in the RO1 (A1032947-11) which indicates that the expression of TROSPA, a tick receptor for OspA, is up regulated upon infection by Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme disease. This presumably facilitates Borrelia colonization of the tick midgut. B. burgdorferi likely modulates the tick transcriptome to ensure its survival and transmission. This aspect of Lyme disease has not been investigated and could open novel venues to vector and disease control. The proposed project aims to broaden the scope of the RO1 and shift the focus beyond TROSPA and OspA. Using cDNA arrays the global changes that occur in the tick salivary gland transcriptome during the infection and transmission of B. burgdorferi will be defined. The functional significance of these gene products in enabling B. burgdorferi invasion of tick salivary glands and its subsequent transmission will be evaluated by specifically silencing the selected tick genes in vivo, using the RNA interference technology. The results of this project will provide insights into tick-Borrelia interactions and enable identification of novel tick -based targets for blocking transmission of Lyme disease. This study will also serve to develop the infrastructure and genetic tools essential for making rapid progress in the field of tick functional genomics. This investigation may therefore serve to pave the way for elucidation of mechanisms underlying transmission of other tick-borne pathogens.

描述（由申请方提供）：该R21提案基于RO 1（A1032947-11）中的观察结果，其表明TROSPA（OspA的蜱受体）的表达在伯氏疏螺旋体感染后上调（B. burgdorferi），莱姆病的病原体。这可能有助于疏螺旋体在蜱中肠的定殖。B。burgdorferi可能调节蜱的转录组以确保其存活和传播。 莱姆病的这一方面尚未调查，可能为媒介和疾病控制开辟新的途径。拟议的项目旨在扩大RO 1的范围，并将重点转移到TROSPA和OspA之外。利用cDNA微阵列技术研究了B.将定义Burgdorferi。这些基因产物在使B。将通过使用RNA干扰技术在体内特异性沉默所选蜱基因来评估蜱唾液腺中的伯氏螺旋体入侵及其随后的传播。该项目的结果将提供对蜱-疏螺旋体相互作用的深入了解，并能够鉴定用于阻断莱姆病传播的新的基于蜱的靶标。这项研究还将有助于开发在蜱功能基因组学领域取得快速进展所必需的基础设施和遗传工具。因此，这项调查可能有助于为阐明其他蜱传病原体传播的机制铺平道路。