Opening up Anopheles funestus to functional genetics and the study of insecticide resistance

开启按蚊的功能遗传学和杀虫剂抗性研究

• 批准号: MR/Y002008/1
• 负责人: Tony Nolan
• 金额: $ 72.98万
• 依托单位: Liverpool School of Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY002008%2F1
• 关键词: Opening; up; Anopheles; funestus; functional

A way to introduce precise genetic changes into an organism is essential for understanding how genes determine key biological characteristics. In the case of mosquito vectors such a technology can allow us to understand the genetic nature of traits that make it such a resilient transmitter of the malaria parasite. Half the world's population are at risk from malaria every year and, despite recent interventions that have had some success, close to half a million people die, most of these children. Anopheles funestus is a significant vector of malaria in many areas of sub-Saharan Africa, often being the dominant species responsible for the majority of transmission in some areas. Despite this, it is relatively poorly studied in the lab, in part because it can be difficult to rear in the laboratory, in part because a technology to genetically transform it - i.e. manipulate its genes to see what effect they have - has yet to be developed. This project will bring together two research teams with unique and complementary experience in the rearing of Anopheles funestus and in genetic transformation of mosquitoes, respectively. We will establish new laboratory colonies of A. funestus, providing varied genetic populations as resource for the scientific community. We will use precise genome editing tools, such as CRISPR, which can function like a precise pair of molecular scissors to cut almost any mosquito DNA sequence of choice to introduce desired sequence changes there. Such a technology permits confirmation of the role of genetic sequences that might previously have been associated with important traits that determine the ability of this mosquito to transmit malaria. The focus of this research proposal will be to understand the genetic basis of insecticide resistance, which is currently jeopardising the gains achieved to date by using insecticide-treated nets and indoor spraying of insecticides. An understanding of the mechanism of resistance will enhance mosquito control through: 1) allowing a quantification of the different genetic contributions to resistance; 2) molecular screening to detect early the emergence of insecticide resistance and in a high throughput fashion; 3) adaptive rotation of insecticide classes in response to mechanism of resistance emerging, in order to prolong the utility of a given insecticide class 4) a comparison of the origins of insecticide resistance among Anopheles funestus and Anopheles gambiae

将精确遗传变化引入生物体的一种方法对于理解基因如何确定关键生物学特征至关重要。对于蚊子向量，这种技术可以使我们能够理解使其成为疟原虫寄生虫的弹性发射器的遗传性质。每年有一半的世界人口都有疟疾的危险，尽管最近的干预措施取得了一些成功，但近一百万人死亡，大多数这些孩子。在撒哈拉以南非洲的许多地区，Anopheles Funestus是疟疾的重要媒介，通常是负责某些地区大多数传播的主要物种。尽管如此，它在实验室中对其进行了相对较差的研究，部分原因是它可能很难在实验室中进行累积，部分原因是一种可以转化遗传的技术 - 即操纵其基因以查看其具有什么影响 - 尚未开发出来。该项目将分别在饲养小动脉群和蚊子的遗传转化方面汇集两个具有独特和互补经验的研究团队。我们将建立新的Funestus实验室殖民地，为科学界提供各种遗传人群。我们将使用精确的基因组编辑工具，例如CRISPR，它们可以像精确的分子剪刀一样起作用，以切割几乎所有选择的蚊子DNA序列，以引入那里所需的序列变化。这样的技术允许确认遗传序列的作用，这些遗传序列以前可能与确定这种蚊子传播疟疾能力的重要特征有关。这项研究建议的重点是了解杀虫剂耐药性的遗传基础，目前通过使用经过杀虫剂处理的网和对杀虫剂的室内喷雾来危害迄今为止所取得的收益。对抵抗机制的理解将通过以下方式增强蚊子控制：1）允许对抗性的不同遗传贡献进行定量； 2）分子筛选以早期检测杀虫剂耐药性和高吞吐量的出现； 3）杀虫剂类别的自适应旋转，以响应抗抗性机制，以延长给定杀虫剂类的效用4）比较了虫害中的杀虫剂耐药性的起源，而巨虫和甲壳虫的gambiae gambiae