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/文摘

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