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

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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.