Genetic Studies of African Anopheles Vectors of Malaria

疟疾非洲按蚊媒介的遗传学研究

• 批准号: 7347005
• 负责人: Jeffrey R POWELL
• 金额: $ 33.92万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7347005
• 关键词: Address; Affect; Africa; Africa South of the Sahara; African; Amino Acid Substitution; Amino Acids; Anopheles Genus; Anopheles gambiae; Complex; Condition; Culicidae; Development; Disease; Event; Evolution; Genes; Genetic; Goals; Health; Human; Immune; Immune response; Immune system; Immunity; Infection; Infection Control; Insecta; Knowledge; Laboratories; Lead; Left; Malaria; Methodology; Molecular Evolution; Mosquito Control; Natural Immunity; Numbers; Parasites; Pattern; Plasmodium; Plasmodium falciparum; Population; Proteins; Research Personnel; Rest; Series; Side; System; Time; Work; concept; fitness; genetic manipulation; killings; response; transmission process; vector; vector control

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.

描述（由研究者提供）：疟疾仍然是撒哈拉以南非洲几乎所有地区的主要健康问题。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最致命的人类疟疾形式（由恶性疟原虫引起）的按蚊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。在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。我们建议在所有四种情况下研究蚊子的先天免疫基因。在本申请期间，我们可以检查约25种蚊子中的约25至30个基因，包括载体和作为对照的密切相关的非载体。其目标是发现哪些基因特异性地进化以应对恶性疟原虫感染。一旦确定蚊子基因与恶性疟原虫感染的特异性共同进化有关，我们将进行一系列分析研究，以检测所涉及的响应基因的特定区域。是否相同的基因和/或基因区域在四个不同的试验中反应相似，或者在每种情况下的进化反应是否是独特的问题将得到解决。对这些基因的鉴定可以导致对它们进行操纵，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完整，从而增强被操纵的蚊子的适应性。用这样的菌株替换天然载体群体需要菌株具有高适应性。