Unravelling the role of the male accessory glands in the fertility of the malaria mosquito Anopheles gambiae

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Mosquitoes represent a major threat for human health, as they transmit a variety of infectious diseases that cause the death and suffering of millions of people each year. Among the most prominent infectious diseases is malaria, which is transmitted exclusively by mosquitoes of the Anopheles genus. Current strategies aimed at tackling this disease rely extensively on the control of vector populations in the field, mainly through the use of insecticide indoor residual sprays and insecticide-impregnated bednets. However, insurgence of resistance in mosquitoes and the lack of novel insecticidal compounds are major hurdles in the fight against malaria, and novel ideas and tools are urgently needed. This proposal focuses on the reproductive biology of the species of mosquito primarily responsible for the transmission of malaria in Africa, known as Anopheles gambiae. An. gambiae mosquitoes mate only once in their lifetime, which means that disrupting the reproductive process offers a good way of dramatically reducing natural populations in Africa. When they mate, the male mosquito transfers sperm to the female and then afterwards transfers a coagulated mass of proteins and seminal fluids known as a mating plug, which is formed in the male accessory glands (MAGs), the mosquito equivalent of the human prostate. The MAGs have been shown by a number of studies to play a very important role in An. gambiae fertility. Transfer of MAG secretions (mainly proteins and lipids) to female mosquitoes has been shown to reduce the female willingness to mate again. Furthermore, our previous studies have shown that transfer of the mating plug is essential for the correct storage of sperm in the female, and hence for female fertility. A deeper knowledge of factors and mechanisms shaping the function of the MAGs would undoubtedly provide novel tools and ideas for the control of mosquito populations in the field through the manipulation of their fertility. As an example, if molecular mechanisms ensuring male fertility were identified, then we could design chemicals to inhibit such mechanisms that could be delivered to field mosquitoes in order to limit their reproductive output. In this project we will perform a detailed analysis of the MAGs, unravelling their functions in regulating mosquito reproductive success. In particular, we will assess whether the MAGs are regulating male behaviour, and we will analyse the roles in fertility of small peptide hormones produced in these reproductive organs. The results obtained here will remarkably improve our knowledge of the reproductive processes occurring in Anopheles mosquitoes, and will provide us with tremendous opportunities to translate this knowledge into practical tools for vector control. To achieve our goals, we will validate the results obtained in the laboratory in field mosquitoes, in collaboration with Professor Dan Masiga, from the International Centre of Insect Physiology and Ecology (ICIPE), Kenya. Strong collaborative links are already established between our groups within the framework of EU projects and in the form of a joint PhD studentship. Our study will focus on An. gambiae mosquitoes, however it could subsequently be extended to other insect pests of medical and agricultural importance. We anticipate that this project will have a profound impact on malaria research, and will contribute to the training and scientific excellence of the next generation of scientists.