Mechanisms of mosquito gut homeostasis and the role of NF-kappaB signalling

与人类肠道相似，蚊子的肠道含有庞大而复杂的细菌群落。雌蚊消化道中的细菌数量在摄入血粉后急剧增加。我们最近已经表明，由细菌增加引起的蚊子肠道的强烈免疫反应对于恢复原始肠道条件（稳态）非常重要，并且还攻击和减少摄入的动物和人类血液传播的病原体（如疟疾寄生虫和病毒）的数量。这些发现突出了肠道微生物群在蚊子传播病原体能力中的重要性，并使我们假设干扰蚊子肠道及其微生物群之间的相互作用可能会导致疾病传播控制的新方法。该项目旨在阐明控制蚊子肠道细菌的分子机制。由于遗传变异，不同蚊子的肠道细菌能力不同。我们将利用这种变异来识别参与与肠道细菌相互作用的基因，然后对这些基因进行测序，以检查它们对肠道细菌群落的特定影响。我们以前的研究表明，识别肽聚糖的蛋白质是细菌细胞壁的重要结构成分，对于抵抗肠道细菌的防御反应很重要。它还表明，该受体通过肽聚糖的定量传感来控制细菌的水平，并严格调节防御反应的激活。我们将使用分子和细胞生物学技术来研究这一新的假设。

Similar to the human intestinal tract, the mosquito gut contains large and complex bacterial communities. The numbers of bacteria in the female mosquito gut increase drastically after ingestion of a bloodmeal. We have recently shown that strong immune reactions of the mosquito gut elicited by the bacterial increase are important in restoring the original gut conditions (homeostasis), and also attack and reduce the numbers of ingested animal and human blood-borne pathogens such as malaria parasites and viruses. These findings highlight the importance of the gut microbiota in the capacity of mosquitoes to transmit pathogens and led us postulate that interfering with the interactions between the mosquito gut and its microbiota could lead to new approaches for disease transmission control. This project aims to characterise the molecular mechanisms involved in the control of mosquito gut bacteria. The capacity to harbour gut bacteria differs from one mosquito to another due to genetic variation. We will take advantage of this variation to identify genes that are involved in the interactions with gut bacteria, and then inactivate each of these genes to examine their specific effects on the gut bacterial communities. Our previous research has shown that a protein recognising peptidoglycan, an important structural component of the bacterial cell wall, is important for defence reactions against gut bacteria. It also suggested that this receptor controls the levels of bacteria by quantitative sensing of peptidoglycan and tightly regulates activation of defence reactions. We will investigate this novel hypothesis using molecular and cell biological techniques.