Causes and consequences of variation in parasite traits

了解寄生虫的进化生态学对于解释临床结果和预测寄生虫对医疗和公共卫生干预措施的反应非常重要。实现这一理解需要确定寄生虫引起疾病和传播能力的基础特征，并解释寄生虫物种或基因型之间这些特征的变化。寄生虫的生活越来越被认为是复杂的：许多寄生虫在多种环境中度过时间，包括不同的宿主和媒介物种，并面临着各种挑战，如宿主内的竞争对手或媒介的变化。所有这些都意味着，要确定寄生虫的特征为什么“是它们现在的样子”，可能需要在寄生虫和人类之间的直接相互作用之外进行思考。作为一个说明性的例子，细菌中的一些抗生素抗性基因比抗生素的出现早了几千年，这是因为细菌在外部环境中相互竞争使用化学上相似的化合物。因此，研究寄生虫性状的一个重要目的是预测哪些已经存在且似乎具有其他目的的性状恰好可以让寄生虫在很短的时间内减轻我们控制工作的影响。 这项资助旨在通过解决三个基本问题来全面了解疟疾寄生虫的进化生态学：1）蚊子媒介中的生命是否会改变宿主中表达的疟疾寄生虫特征的进化？2)在高传播环境中，疟疾寄生虫经常与其他基因型共享宿主，是否有证据表明这些寄生虫进化得更具毒性（进化理论的标准预测）？3）什么样的寄生虫特征可以解释实验性啮齿动物疟疾感染中观察到的药物敏感性变化和疫苗逃逸的演变？虽然这项提案的重点是疟疾寄生虫，但我们发现的进化和生态学原理将具有更广泛的影响，提高对疾病的理解，并为生物医学提供新的见解。这项研究还将为高素质的学生和博士后研究员提供生态学和进化生物学方面的广泛培训，以及适用于工业，生物医学，政府和学术界的数学，统计和计算技术。

Understanding the evolutionary ecology of parasites is important for explaining clinical outcomes and predicting how parasites will respond to medical and public health interventions. Achieving this understanding requires identifying traits that underlie the ability of parasites to cause disease and get transmitted, and explaining variation in those traits across parasite species or genotypes. The lives of parasites are increasingly recognized as complex: many parasites spend time in multiple environments, including diverse host and vector species, and are faced with a variety of challenges like competitors within a host or changing availability of vectors. All of this means that determining why parasite traits “are the way they are” may require thinking outside of the direct interactions between parasites and humans. As one illustrative example, some antibiotic resistance genes in bacteria predate the advent of antibiotics by several millennia, owing to the fact that bacteria use chemically similar compounds in competition with each other in the external environment. An important aim of investigating parasite traits is therefore predicting which traits, that already exist and appear to serve some other purpose, will coincidentally allow parasites to mitigate the effects of our control efforts on very short timescales. This grant seeks a holistic understanding of the evolutionary ecology of malaria parasites by addressing three fundamental questions: 1) does life in a mosquito vector alter the evolution of malaria parasite traits that are expressed in a host? 2) In high-transmission settings, where malaria parasites frequently share their host with other genotypes, is there evidence that these parasites have evolved to be more virulent (a standard prediction of evolutionary theory)? And 3) what parasite traits explain observed variation in sensitivity to drugs and the evolution of vaccine-escape in experimental rodent malaria infections? While the focus of this proposal is on malaria parasites, the evolutionary and ecological principles we uncover will have wider implications, improving understanding of disease and offering new insight to biomedicine. This research will also provide high caliber students and postdoctoral fellows with broad training in ecology and evolutionary biology, as well mathematical, statistical, and computational techniques that are applicable to industry, biomedicine, government, and academia.