Resource availability and the evolution of host resistance to parasites: within individuals, trade-off shapes and the genetic basis of resistance

研究背景最近的流行病继续强调传染性疾病如SARS对人类健康和农业生产的重要性。同样清楚的是，即使不是全部，大多数动物、植物和微生物都受到各种各样传染病的感染。这些疾病无论是由细菌、病毒还是线虫引起的，往往对其宿主造成重大伤害。特别是它们可能缩短它们的寿命或减少受感染个体宿主所能产生的后代的数量。结果，个体进化出了各种各样的抵抗感染的方式。他们可以避免被感染，更快地恢复或减少宿主对他们造成的伤害。如果我们要在自然和农业系统中管理疾病，了解决定耐药性的因素至关重要。特别是在自然环境中，在任何特定时间、任何特定地点可获得的资源具有相当大的可变性。由于个人的资源有限，他们必须将资源分配给相互竞争的需求——例如维持身体状况——这种资源的变化对疾病的影响至关重要。因此，了解资源在耐药性进化中所起的作用是很重要的。目的和目标为了了解资源对免疫的作用，有必要在资源改变的情况下进行实验。这就需要使用一种模型经验系统，在这种系统中可以实现对资源的必要控制。我们提出了一套详细的实验使用这样的模型基于昆虫和它的病毒病原体。首先，我们将根据近年来测序技术的进步开发一些遗传工具。我们将测量免疫功能的成本和收益的遗传基础。我们的方法是控制昆虫的繁殖，这样我们就可以检查家庭内的免疫功能。这使我们能够确定有多少变异是由于亲缘关系和遗传造成的。通过在不同的环境中进行这些实验，我们可以弄清楚基因变异的性质在不同的环境下是如何变化的。我们还将研究在单个个体感染的时间过程中，不同资源环境下的免疫反应是如何变化的。最后，我们将允许在实验室中在良好和恶劣的环境下进行进化，看看发生的抗性是否由于不同的机制而产生。潜在的应用和益处这项工作的基本应用是，它将帮助我们了解免疫力是如何进化的。这样就可以减少疾病对自然系统和人类造成的伤害。特别是，我们的研究结果可能使我们能够预测如何通过改变饮食来更好地控制疾病。我们也将有更好的机会预测正在发生的人为环境变化何时以及如何导致疾病暴发。人类活动正在改变许多环境，并经常导致可供宿主使用的资源减少。因此，我们需要更好地了解这对疾病的影响，以便管理和保护自然资源。我们使用的实验室模型系统是一种主要的农业害虫，因此我们的结果也有可能帮助控制它。

Context of the researchRecent epidemics continue to emphasise the importance of infectious disease such as SARS to human health and agricultural production. It is also clear that most if not all animals, plants and microbes are infected by a wide variety of infectious diseases. These diseases whether they are caused by bacteria, viruses or nematode worms often cause significant harm to their hosts. In particular they may shorten their life or reduce the number of offspring that the infected individual host can produce. As a consequence individuals have evolved a wide variety of ways of resisting infection. They can avoid becoming infected, recover more quickly or reduce the damage that the host causes them. Understanding what factors determine resistance is vital if we are to manage disease in natural and agricultural systems. In particular, in natural environments there is considerable variability in the resources that are available at any particular time in any given place. Since individuals have limited resources and they must allocate them to competing demands - such as the maintenance of body condition - such variation in resources is critical to the impact of disease. It is therefore important to understand the role that resources play in the evolution of resistance.Aims and objectivesIn order to understand the role that resources have on immunity it is necessary to carry out experiments where resources are altered. This requires the use of a model empirical system where the necessary control of resources can be achieved. We propose a set of detailed experiments using such a model based on an insect and its viral pathogen. First we will develop a number of genetic tools based on the advances in sequencing technology that have occurred in recent years. We will measure the genetic basis of the costs and benefits of immune function. Our approach is to control the breeding of the insect so that we can examine the immune function within families. This allows us to determine how much of the variation is due to relatedness and therefore genetics. By carrying out these experiments in different environments, we can work out how the nature of genetic variation changes under different circumstances. We will also look at how the immune response changes under different resource environments during the time course of the infection within single individuals. Finally we will allow evolution to occur in the laboratory under good and bad environments and see if the resistance that occurs comes about due to different mechanisms. Potential applications and benefitsThe fundamental application of this work is that it will help us to understand how immunity evolve. This can then reduce the harm that disease causes in natural systems and to people. In particular our results may enable us to predict how we can better manage disease through changes in diet. We will also have a better chance of predicting when and how the man made changes in the environment that are occurring may lead to disease outbreaks. Human activity is changing many environments and often leading to a reduction in the available resources for hosts. As such we need a better understanding of the implications of this to disease in order to manage and conserve natural resources. The laboratory model system that we use is a major agricultural pest and therefore our results also have the potential to help in its control.