Combining Aedes aegypti genomics and modeling to improve gene drive strategies and our understanding of resistance evolution

结合埃及伊蚊基因组学和建模来改进基因驱动策略和我们对抗性进化的理解

• 批准号: 10401825
• 负责人: FRED GOULD
• 金额: $ 37.02万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-05 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401825
• 关键词: Adult; Aedes; Algorithmic Analysis; Arbovirus Infections; Arboviruses; Candidate Disease Gene; Cities; Communities; Country; Culicidae; DNA; DNA Sequence; Data; Dengue; Development; Disease; Effectiveness; Emergency Situation; Epidemic; Evolution; Fright; Future; Generations; Genes; Genetic; Genetic Drift; Genome; Genomics; Genotype; Geography; Goals; Grant; Health system; Human; Incidence; Individual; Insecta; Insecticide Resistance; Insecticides; Location; Measures; Methods; Mexico; Modeling; Monitor; Mosquito Control; Movement; Neighborhoods; Outcome; Output; Partner in relationship; Pattern; Peru; Population; Population Dynamics; Population Genetics; Population Sizes; Public Health; Puerto Rico; RNA; Research; Resistance; Sampling; Structure; Testing; Time; Uncertainty; Work; Yellow fever virus; ZIKA; base; chikungunya; combat; density; gene drive system; genetic pedigree; genome-wide; genomic data; improved; novel; novel strategies; pathogen; pyrethroid; resistance allele; resistance gene; sample archive; vector; vector control

Summary/Abstract The mosquito, Aedes aegypti, is a primary vector for dengue, chikungunya, Zika, and urban yellow fever viruses. Dengue has become the most important human arthropod-borne viral infection worldwide. Each of these pathogens can be associated with explosive epidemics, where high disease incidence and public fear combine to overwhelm health systems. Public health departments often react with emergency insecticide-based vector control measures. Spraying with pyrethroid insecticides is the main approach used for adult Ae. aegypti control in many countries. While the impact of this spraying on disease suppression has been questioned, there is no doubt that the repeated use of pyrethroid sprays has caused geographically widespread evolution of resistance and loss of impact of pyrethroids on mosquito densities. Over 10,000 archived samples of Ae. aegypti collected from Iquitos, Peru since 2000 are being held at -80˚C and have intact DNA. Over this period of time pyrethroid spray efficacy in Iquitos has declined substantially due to resistance. These samples will be used to assess patterns of spatial and temporal change in genes associated with pyrethroid resistance and in genomic differentiation. With this genomic information it will be possible to test hypotheses about the dynamics of pyrethroid resistance evolution and hypotheses about the efficacy of new gene drive strategies that could suppress Ae. aegypti populations or lower the ability of the mosquito to transmit pathogens. These tests will be enabled by new algorithms for analysis of mating structure. A spatially explicit, stochastic model of Ae. aegypti population dynamics and genetics will be parameterized with the new genomic data and used to predict future dynamics of insecticide resistance and gene drives. Outcomes of this work will provide research, regulatory, and management communities with information needed to more accurately predict dynamics of a variety of gene drive strategies as well as the spread of resistance to insecticides in this arbovirus vector. We have three Aims in this project that will together result in these more accurate predictions: AIM 1. Use single gene and genome-wide methods to characterize temporal and spatial genetic differentiation in Ae. aegypti populations AIM 2. Use the data from Aim 1 to develop a more accurate understanding of the movement and mating structure of Ae. aegypti AIM 3. Incorporate findings from Aim 2 into a detailed Ae. aegypti model, and use it to test a variety of existing and new strategies for gene drives as well as for monitoring evolution of resistance in Ae. aegypti to use of gene drives and insecticides. !

摘要/摘要 埃及伊蚊是登革热、基孔肯雅热、寨卡病毒和城市黄蜂的主要传播媒介 发烧病毒已成为最重要的人类节肢动物传播的病毒感染。 在世界范围内，这些病原体中的每一种都可能与爆发性流行病有关。 疾病发病率和公众恐惧结合在一起，让公共卫生部门不堪重负。 喷洒拟除虫菊酯 杀虫剂是许多国家控制埃及伊蚊成虫的主要方法。 这种喷洒对抑制疾病的影响受到质疑，但毫无疑问 重复使用拟除虫菊酯喷雾剂已导致地理上广泛的耐药性进化 拟除虫菊酯对蚊子密度的影响消失。 自 2000 年以来从秘鲁伊基托斯收集的 10,000 多个埃及伊蚊存档样本正在被保存。 在 -80°C 下保存并具有完整的 DNA 在此期间，拟除虫菊酯喷洒在伊基托斯中的功效已得到改善。 这些样本将用于评估空间模式 以及与拟除虫菊酯抗性和基因组分化相关的基因的时间变化。 有了这些基因组信息，就有可能测试有关拟除虫菊酯动力学的假设 抗性进化和关于新基因驱动策略功效的假设 抑制埃及伊蚊种群或降低蚊子传播病原体的能力。 测试将通过新的交配结构分析算法来实现。 埃及伊蚊种群动态和遗传学的随机模型将用 新的基因组数据，用于预测杀虫剂抗性和基因驱动的未来动态。 这项工作的成果将为研究、监管和管理界提供 更准确地预测各种基因驱动策略的动态所需的信息 随着这种虫媒病毒载体对杀虫剂的抗药性的传播。 我们在这个项目中有三个目标，这些目标将共同带来这些更准确的预测： 目标 1. 使用单基因和全基因组方法来表征时间和空间遗传学 埃及伊蚊群体的分化 目标 2. 使用目标 1 中的数据更准确地了解运动和交配 埃及伊蚊的结构 AIM 3. 将 Aim 2 的发现纳入详细的埃及伊蚊模型中，并用它来测试各种不同的埃及伊蚊。 现有的和新的基因驱动策略以及监测伊蚊抗性进化的策略。 埃及伊蚊使用基因驱动和杀虫剂。 ！

项目成果

Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex.

• DOI: 10.1146/annurev-ecolsys-031120-101013
• 发表时间: 2020-11
• 期刊: Annual review of ecology, evolution, and systematics
• 作者: Dhole S;Lloyd AL;Gould F
• 通讯作者: Gould F

CRISPR/Cas9-based split homing gene drive targeting doublesex for population suppression of the global fruit pest Drosophila suzukii.

• DOI: 10.1073/pnas.2301525120
• 发表时间: 2023-06-20
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Yadav, Amarish K.;Butler, Cole;Yamamoto, Akihiko;Patil, Anandrao A.;Lloyd, Alun L.;Scott, Maxwell J.
• 通讯作者: Scott, Maxwell J.

The impact of local population genetic background on the spread of the selfish element Medea-1 in red flour beetles.

当地群体遗传背景对自私元素Medea-1在红粉甲虫中传播的影响。

• DOI: 10.1002/ece3.5946
• 发表时间: 2020
• 期刊: Ecology and evolution
• 影响因子: 2.6
• 作者: Cash,SarahA;Robert,MichaelA;Lorenzen,MarcéD;Gould,Fred
• 通讯作者: Gould,Fred

After the honeymoon, the divorce: Unexpected outcomes of disease control measures against endemic infections.

• DOI: 10.1371/journal.pcbi.1008292
• 发表时间: 2020-10
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Hollingsworth B;Okamoto KW;Lloyd AL
• 通讯作者: Lloyd AL

A critical assessment of the detailed Aedes aegypti simulation model Skeeter Buster 2 using field experiments of indoor insecticidal control in Iquitos, Peru.

• DOI: 10.1371/journal.pntd.0010863
• 发表时间: 2022-12
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8