疟疾是重要的媒传疾病。已有研究显示蚊媒的miRNA可参与调控对病原体的抗感染防御，但目前尚缺乏关于其参与调控按蚊对疟原虫易感性的相关分子机制研究。本课题组前期研究发现，大劣按蚊感染疟原虫后其miRNA及mRNA表达谱均出现显著差异表达，其中miR-2944a-5p感染后表达水平下调最显著，其预测靶基因TSL是MAPK信号通路中的重要成员，呈显著上调。研究报导MAPK信号通路的活化可以促进按蚊对疟原虫易感性。据此，我们提出科学假设：miR-2944a-5p是重要的易感性相关miRNA，可通过靶向TSL基因调控MAPK信号通路促进按蚊对疟原虫易感性。本研究拟通过对miR-2944a-5p及其靶基因TSL进行表达及功能分析，并利用RNA干扰、报告基因检测、western等实验技术手段在体内外进行验证。本研究不仅有助于阐释媒介-病原体的相互作用机制，同时也能够为新的媒介控制策略的开发提供新的思路。

Malaria is one of the most serious vector-borne infectious diseases. Anopheles dirus is the important malaria vector in China. It is of great significance to unveil and clarify the interactions between the parasite and vector at the molecular level for the prevention and elimination of malaria. microRNAs have been proved to have critical physiological and pathological biology functions, serving as important regulatory factors at the post-transcription level to regulate gene expression. We have performed a genome-wide analysis of miRNA-mRNA interactions and discovered that the transcripts of some mosquito genes are differentially regulated by certain miRNAs in response to plasmodium berghei infection. Among them, miR-2944a-5p was the most down-regulated miRNA, and its predicted target gene TSL (Torso-like) was significantly up-regulated. Shanu Jain et al reported that miRNA2944 was expressed significantly in blood fed Anopheles stephensi (42 h), and it was also significantly down-regulated in iBF (infected blood fed) 5 d when compared with iBF 42 h. TSL is the initial member of MAPK (mitogen-activated protein kinase) signaling pathway which is critical to regulating both innate immunity and metabolism during infection. Activation of MAPK signaling pathway in the mosquito midgut could facilitate parasite infection. On the basis of comprehensive analysis of literatures and our previous work results, we proposed the hypothesis that miR-2944a-5p is an important susceptibility-related miRNA, which target TSL and related MAPK signaling pathways to promote the susceptibility of Anopheles dirus to Plasmodium parasite. We will study the function of miR-2944a-5p and its target genes TSL in Anopheles dirus physiology and immunity. We will also analyze the tissue specific expression and temporal expression pattern of them. We expect to clarify the relevant molecular mechanisms of Anopheles dirus miR-2944a-5p target TSL involved in the MAPK signaling pathway to regulate the susceptibility to parasite from the post-transcription level through the RNA interference, Luciferase reporter assay, western, and other experimental technologies in vivo and in vitro. Our proposed study will not only help interpreter pathogen-vector interactions, but also can provide new sight for the development of novel vector control strategies.