Genetic Studies of African Anopheles Vectors of Malaria

描述(由调查员提供)：疟疾仍然是几乎所有撒哈拉以南非洲地区的一个主要健康问题。控制这种致命疾病的主要方式是控制传播它的蚊子。这里提出的工作将有助于我们了解通过控制传播由恶性疟原虫引起的最致命的人类形式疟疾的按蚊物种来控制疟疾传播的方法。该项目采用进化的方法来识别蚊子先天免疫系统的基因，这些基因可以杀死或抑制疟疾寄生虫的感染。撒哈拉以南非洲有四例按蚊感染了恶性疟原虫，并成为人类的主要媒介。我们建议研究所有四种情况下的蚊子先天免疫基因。在这一应用期间，我们可以检查大约25种蚊子的25到30个基因的数量级，这些蚊子既有媒介，也有密切相关的非媒介作为对照。其目标是发现哪些基因在应对恶性疟原虫感染时发生了特定的进化。一旦确定蚊子基因与恶性疟原虫感染的特定协同进化有关，我们将进行一系列分析研究，以检测涉及的反应基因的特定区域。同样的基因和/或基因区域在四个不同的试验中是否做出类似的反应，或者在每个情况下进化反应是否是唯一的，这些问题将被解决。对这些基因的识别可以导致对它们的操纵，以产生不能传播恶性疟原虫的蚊子，同时保持免疫系统的其余部分不变，从而增强被操纵的蚊子的适应能力。用这样的菌株替换自然媒介种群需要菌株具有很高的适应性。

DESCRIPTION (provided by investigator): Malaria remains a major health problem throughout virtually all of sub-Saharan Africa. The major manner in which this deadly disease is controlled is through control of the mosquitoes that transmit it. The work proposed here will contribute to our knowledge of ways to control malaria transmission through control of the species of Anopheles that transmit the deadliest human form of malaria, that caused by Plasmodium falciparum. The project takes an evolutionary approach to identifying genes of the innate immune system of the mosquitoes that act to kill or inhibit infection by the malaria parasite. There are four cases of Anopheles in sub-Saharan Africa having picked up P. falciparum and become major vectors to humans. We propose to study mosquito innate immune genes in all four cases. During the period of this application we can examine on the order of 25 to 30 genes in about 25 species of mosquitoes, both vectors and closely related non-vectors that act as controls. The goal is to discover what genes specifically evolve in response to falciparum infection. Once mosquito genes are identified to be implicated in specifically coevolving with falciparum infections, we will carry out a series of analytical studies to detect specific regions of the responding genes that are involved. Questions of whether the same genes and/or gene regions respond similarly in four different trials or whether in each case the evolutionary response is unique will be addressed. Identification of such genes can lead to manipulation of them to produce mosquitoes incapable of transmitting falciparum while leaving the rest of the immune system intact, thus enhancing the fitness of the manipulated mosquitoes. Replacing natural vector populations with such strains require that the strain have high fitness.