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

蚊子是人类健康的主要威胁，因为它们传播各种传染病，每年造成数百万人死亡和痛苦。最主要的传染病之一是疟疾，它完全由按蚊属的蚊子传播。目前旨在防治这种疾病的战略主要依靠在现场控制病媒种群，主要是通过使用杀虫剂室内残留喷剂和浸渍杀虫剂的蚊帐。然而，蚊子耐药性的增加和缺乏新的杀虫化合物是抗击疟疾的主要障碍，迫切需要新的想法和工具。这一建议的重点是主要负责非洲疟疾传播的冈比亚按蚊的生殖生物学。一个。冈比亚蚊子一生中只交配一次，这意味着破坏繁殖过程是大幅减少非洲自然种群的好方法。当它们交配时，雄蚊将精子转移给雌蚊，然后再转移一种凝固的蛋白质和精液，这种蛋白质和精液在雄蚊的副腺（MAGs）中形成，相当于人类的前列腺。许多研究表明，mag在An中起着非常重要的作用。冈比亚按蚊的生育能力。将MAG分泌物（主要是蛋白质和脂质）转移到雌蚊体内，已被证明会降低雌蚊再次交配的意愿。此外，我们之前的研究已经表明，交配塞的转移对于精子在雌性体内的正确储存至关重要，因此对于雌性的生育能力至关重要。对形成mag功能的因素和机制的深入了解无疑将为通过控制蚊子的繁殖能力来控制蚊子种群提供新的工具和思路。举个例子，如果确定了确保雄性生殖能力的分子机制，那么我们就可以设计化学物质来抑制这种机制，这种机制可以传递给野外蚊子，以限制它们的生殖产出。在这个项目中，我们将对mag进行详细的分析，揭示它们在调节蚊子繁殖成功率方面的功能。特别是，我们将评估mag是否在调节男性行为，我们将分析这些生殖器官产生的小肽激素在生育中的作用。这里获得的结果将显著提高我们对按蚊繁殖过程的认识，并将为我们提供巨大的机会，将这些知识转化为媒介控制的实用工具。为了实现我们的目标，我们将与肯尼亚国际昆虫生理学和生态学中心（ICIPE）的Dan Masiga教授合作，在野外蚊子中验证在实验室获得的结果。在欧盟项目框架内，我们的小组之间已经建立了强有力的合作关系，并以联合博士研究生的形式建立了合作关系。我们的研究将集中在An。冈比亚蚊，然而，它可以随后扩展到其他具有医疗和农业重要性的害虫。我们预计这个项目将对疟疾研究产生深远的影响，并将有助于培养下一代科学家并使他们在科学上取得卓越成就。

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.