Explaining the complex lives of parasites: within-host dynamics, parasite plasticity, and life history evolution

尽管对传染病进行了几个世纪的研究，但对重要的生态和进化问题仍没有令人满意的答案，例如：哪些因素塑造了决定对宿主造成的伤害和传染性的寄生虫特征的进化？寄生虫和宿主之间的相互作用如何以及为什么在不同的寄生虫物种之间存在差异，也就是说，为什么有些疾病比较严重，而另一些则不那么严重？药物或疫苗可能如何影响寄生虫的特征及其与宿主的相互作用？全球疾病统计数据突出了回答这些问题的重要性：传染病目前在全世界占死亡人数的六分之一，在发展中地区占死亡人数的二分之一(世卫组织)。此外，在加拿大，我们面临着来自耐药细菌(例如MRSA)的日益增长的威胁，这是生态相互作用和进化反应的结果。因此，更好地了解寄生虫进化生态学对于设计有效的治疗和控制策略至关重要。进化生态学的一个关键见解是，寄生虫是比人们通常认为的更复杂的有机体--它们能够检测到环境的变化，并相应地调整策略。通过将数学模型与实验数据相结合，我的研究项目调查了这种“表型可塑性”的原因、结果和限制。在接下来的五年里，我的团队将确定(1)寄生虫特征的变化对宿主内的疾病模式有什么影响，以及它们是否有助于在寄生虫品系之间观察到的差异，(2)这些变化是否有助于寄生虫应对可变的环境(即这种可塑性是否具有适应性)，以及(3)这种可塑性侵蚀疾病控制努力的潜力是什么。这项研究将培训研究生和本科生掌握适用于工业、生物医学、政府和学术界的数学和统计技术。虽然我们的大部分研究工作将集中在疟疾寄生虫上，但我们发现的进化原理将具有深远的影响，提高对疾病的理解，并为生物医学提供新的见解。

Despite centuries of research into infectious diseases, there are no satisfying answers to important ecological and evolutionary questions, such as: Which factors have shaped the evolution of parasite traits that determine harm caused to hosts and infectiousness? How and why do interactions between parasites and hosts differ across parasite species, i.e., why are some diseases severe and others less so? How might drugs or vaccines affect parasite traits and their interactions with hosts? Global disease statistics highlight the importance of answering these questions: infectious diseases currently account for 1 in 6 deaths worldwide, and 1 in 2 deaths in developing regions (WHO). Further, in Canada we are confronted with an ever-increasing threat from drug resistant bacteria (e.g., MRSA), which are a consequence of ecological interactions and evolutionary responses. Developing a better understanding of parasite evolutionary ecology is therefore critical to designing effective treatment and control strategies. A key insight from evolutionary ecology is that parasites are more sophisticated organisms than they tend to be given credit for - they are able to detect changes in their environment and adjust their strategies accordingly. By integrating mathematical modeling with experimental data, my research program investigates the causes, consequences, and limits of this 'phenotypic plasticity'. Over the next five years, my group will determine (1) what impact changes in parasite traits have on patterns of disease within hosts and whether they contribute to the variation observed across parasite strains, (2) whether these changes help parasites deal with a variable environment (i.e., whether this plasticity is adaptive), and (3) what the potential is for this plasticity to erode disease control efforts. This research will train graduate and undergraduate students in mathematical and statistical techniques that are applicable to industry, biomedicine, government, and academia. While the focus of much of our research effort will be on malaria parasites, the evolutionary principles we uncover will have far reaching implications, improving understanding of disease and offering new insight to biomedicine.