Genetic Studies of African Anopheles Vectors of Malaria

描述（由调查员提供）：疟疾仍然是撒哈拉以南非洲几乎所有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通过控制传播它的蚊子。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疟疾的按蚊种类来控制疟疾传播的方法。该项目采用一种进化方法来鉴定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4例感染了恶性疟原虫并成为人类主要病媒的按蚊病例。我们建议在这四种情况下研究蚊子的先天免疫基因。在此应用期间，我们可以在大约25种蚊子中检测25至30个基因，包括媒介蚊子和作为对照的密切相关的非媒介蚊子。目标是发现哪些基因在恶性疟原虫感染的反应中特异性进化。一旦确定蚊子基因与恶性疟原虫感染特异性共进化有关，我们将开展一系列分析研究，以检测相关响应基因的特定区域。同样的基因和/或基因区域在四种不同的试验中是否有相似的反应，或者在每种情况下是否有独特的进化反应，这些问题将得到解决。鉴定这些基因可以导致对它们进行操纵，使蚊子不能传播恶性疟，同时保持免疫系统的其余部分完好无损，从而增强被操纵蚊子的适应性。用这些菌株替代自然媒介种群要求菌株具有高适应度。

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.