DISSERTATION RESEARCH: The Role of Multiple Infections in the Evolution of Virulence

这项研究建立在实地和实验室工作的基础上，通过实验解决疾病进化的一个中心问题，调查塞伦盖蒂地区多重锥虫感染的流行情况。理论预测，同一宿主动物体内不同寄生虫之间的竞争将导致每种寄生虫的严重程度(毒力)增加，但这一预测缺乏经验支持。为了验证这一预测，小鼠将感染不同品系的布鲁氏锥虫，这是一种具有重大经济和医学意义的原虫寄生虫。三种寄生虫菌株，通过在它们的基因组中引入不同的荧光标记，可以在视觉上区分开来，它们将单独或组合在老鼠身上重复传递。然后，将从混合感染中分离出寄生虫，并将测量它们对小鼠的影响，以确定它们是否像理论预测的那样，在单一感染中进化到比相同寄生虫更高的毒力。拟议实验的智力价值在于为多重感染对寄生虫毒力的影响提供了一个关键测试。由此产生的经验数据将有助于将毒力进化理论建立在更好的基础上。拟议的研究将通过提高我们对寄生虫和疾病动力学的理解而产生更广泛的影响。作为一项国际合作，它还将在美国、欧洲和非洲的机构之间转移知识。

This research builds on field and laboratory work investigating the prevalence of multiple trypanosome infections in the Serengeti by experimentally addressing a central question of disease evolution. Theory predicts that competition among different parasites in one host animal will lead to increased severity (virulence) of each parasite, but empirical support for this prediction is scarce. To test the prediction, mice will be infected with different strains of Trypanosoma brucei, protozoan parasites of great economic and medical importance. Three parasite strains, visually distinguishable by different fluorescent markers introduced into their genomes, will be repeatedly passed through mice alone or in combinations. Parasites will then be isolated from mixed infections and their effect on mice will be measured to determine whether they have evolved to higher virulence than the same parasites in single infections, as theory would predict. The intellectual merit of the proposed experiment is to provide for a critical test of the effect of multiple infections on parasite virulence. The resulting empirical data will help put virulence evolution theory on a better foundation. The proposed research will have broader impact by improving our understanding of parasite and disease dynamics. As an international collaboration it will also transfer knowledge among institutions in the United States, Europe, and Africa.