Tick gene expression- in the context of Lyme disease

描述(由申请人提供)：本R21提案建立在RO1(A1032947-11)中的观察结果的基础上，该RO1中的观察表明，在莱姆病的病原体伯氏疏螺旋体(B.burgdorferi)感染时，OspA的壁虱受体TROSPA的表达上调。这可能有助于疏螺旋体在扁虱中肠的定植。伯氏杆菌可能会调节扁虱转录组，以确保其生存和传播。 莱姆病的这一方面尚未被研究，并可能为媒介和疾病控制开辟新的场所。拟议的项目旨在扩大RO1的范围，并将重点转移到TROSPA和OSPA之外。利用基因芯片，我们将确定在感染和传播伯氏杆菌过程中，壁虱唾液腺转录组中发生的整体变化。我们将利用RNA干扰技术，通过在体内特异性地沉默选定的壁虱基因，来评估这些基因产物在使伯氏杆菌入侵扁虱唾液腺及其随后传播方面的功能意义。该项目的结果将提供对扁虱-疏螺旋体相互作用的见解，并能够识别以扁虱为基础的新靶标来阻断莱姆病的传播。这项研究还将有助于开发在扁虱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，这项研究可能为阐明其他壁虱传播病原体的潜在传播机制铺平道路。

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.