Modeling of Mosquitoes Carrying Transgenes or Genetically Modified Bacteria in Preventing the Transmission of Mosquito-Borne Diseases

在这个项目中，研究人员开发了各种蚊子种群和疾病传播动态的数学模型。这包括转基因蚊子的模型，这种蚊子对蚊媒疾病的感染具有抵抗力，并且具有独特的适应性，其中一些比其他的更有优势。用组合流行病模型研究蚊子间的相互作用动力学，刻画转基因蚊子比非转基因蚊子具有选择性优势的事实，并研究转基因蚊子对疾病传播的影响。对带有不同基因或品系的转基因蚊子进行建模，以及对包括雄性和雌性在内的两性蚊子种群进行建模，也是该项目的一部分。所有模型都从更简单的形式开始，然后逐渐包括更复杂的结构，以更好地描述潜在的生物学。在每个模型类别中，研究人员为出生和死亡函数以及接触率确定不同的公式，这有助于将建模与真实数据联系起来。随着蚊虫种群模型的建立，将结合各种人和蚊子种群的流行病模型来研究蚊媒疾病的传播动力学。这位研究人员还专注于对新开发的副转基因技术进行建模，该技术试图通过转基因共生体，即防止蚊子传播病原体的转基因细菌，从蚊子种群中消除病原体。研究了蚊虫间细菌水平传播和垂直传播的动态及其对疾病传播的影响。目的是了解野生蚊子和携带转基因或转基因细菌的蚊子相互作用的复杂性，并预测释放转基因蚊子的影响。分析和数值模拟相结合，研究了模型的定性和定量特征，包括平衡点的存在性和稳定性，通过分叉存在周期和非周期振荡，以及混沌行为和暂态动力学。模型参数是从真实的生物数据估计或得出的，模型的数学分析涵盖了所有参数区域。生物学的新发展使研究人员能够对蚊子进行基因改造，使它们对疟疾感染或其他蚊子传播的疾病，如登革热和西尼罗河病毒具有抵抗力。最近开发的一种新的副转基因方法使蚊子携带基因修饰的细菌，这种细菌损害了病原体在蚊子中的传播。蚊媒疾病是通过食血蚊子在人与人之间传播的，它们的传播和控制一直是公共卫生的主要问题。在野生蚊子种群中引入改良蚊子可能是控制蚊媒疾病的有效措施。为了探索这种可能性，研究人员与生物学家合作，开发并分析了代表野生和转基因蚊子种群动态的数学模型。这些模型考虑了转基因或转基因细菌通过蚊子种群在多个世代之间的传播，并预测了对疾病传播的影响。他们帮助回答了这样的问题：携带转基因或转基因细菌的蚊子将如何有效地与野生蚊子竞争伴侣，新的抗药性基因或细菌需要多长时间才能渗透到蚊子种群中，以及它在防止疾病传播方面的效果如何。这样，该项目的成果可以为公共卫生措施和疾病预防战略提供有用的指导。

The investigator develops various mathematical models for mosquito populations and disease transmission dynamics in this project. This includes models for transgenic mosquitoes, which are resistant to infection by mosquito-borne diseases, and have distinct fitnesses, some of which have advantages over the others. Combined epidemic models are used to study the interactive dynamics of the mosquitoes, characterizing the fact that transgenic mosquitoes have a selective advantage over non-transgenic mosquitoes, and to investigate the effects of transgenic mosquitoes on the disease transmissions. Modeling of transgenic mosquitoes with various genes or strains, as well as modeling of two-sex mosquito populations including both males and females, is also part of this project. All models start with simpler forms, and gradually include more complex structures to better describe the underlying biology. Within each model category, the investigator determines different formulas for the birth and death functions and the contact rates, which facilitates the ability to connect the modelling with real data. With the population models for the mosquitoes well established, various epidemic models for both human and mosquito populations will be incorporated to study the transmission dynamics of the mosquito-borne diseases. The investigator also focuses on modeling of the newly developed paratransgenic technique, which attempts to eliminate a pathogen from mosquito populations through transgenesis of a symbiont, i.e., a genetically modified bacterium, that prevents the mosquitoes from transmitting the pathogen. The dynamics of horizontal bacteria transmission, as well as vertical transmission between mosquitoes, and their effects on the disease transmissions are investigated. The goal is to understand the complexity of the dynamics of the interacting wild mosquitoes and the mosquitoes carrying transgenes or genetically modified bacteria, and predict the impact of releasing the modified mosquitoes. Analysis and numerical simulation is combined to study qualitative and quantitative features of the models, including existence and stability of equilibria, existence of periodic and aperiodic oscillations through bifurcations, and chaotic behavior and transient dynamics. Model parameters are estimated or derived from real biological data and the mathematical analysis of the models covers all parameter regions.New developments in biology allow researchers to genetically alter mosquitoes so that they are resistant to malaria infection or other mosquito-borne diseases, such as dengue fever and West Nile virus. A more recently developed new paratransgenic approach generates mosquitoes carrying genetically modifies bacteria that impairs in the transmission of pathogens in mosquitoes. The mosquito-borne diseases are transmitted between humans by blood-feeding mosquitoes, and their spread and control have been major concerns for public health. The introduction of modified mosquitoes into wild mosquito populations could be an effective measure in controlling mosquito-borne diseases. To explore this possibility, the investigator, in collaboration with biologists, develops and analyzes mathematical models that represent the population dynamics of wild and transgenic mosquitoes. The models account for the spread of transgenes or genetically modified bacteria through the mosquito population over multiple generations, and predict the impact on the disease transmissions. They help answer such questions as how effectively mosquitoes carrying transgenes or modified bacteria would be able to compete for partners with their wild counterparts, how long it would take for a new resistance gene or bacterium to penetrate the mosquito population, and how effective it would be in preventing the spread of the diseases. In this way, the results of the project can provide useful guidance for public health measures and for disease prevention strategies.