Doctoral Dissertation Research: Comparative analysis of malaria impacts on human and primate evolution

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。人类和非人类灵长类动物都通过基因组的变化进化出了防御疟疾的适应性。本博士论文研究使用比较灵长类动物数据来推进关于灵长类动物与疟疾或类似寄生虫共同进化的知识，包括疟疾如何影响灵长类动物免疫系统的进化以及确定对血期疟疾免疫反应的遗传机制。项目成果可为人类应对疟疾的公共卫生相关研究提供信息。该项目还支持外展工作，重点是通过K-12外展和计算基因组能力建设，增加代表性不足群体对STEM研究的参与。利用比较功能和进化基因组学方法，这组科学家确定了灵长类动物在疟疾感染反应中差异表达的基因和途径，包括那些与疟疾反应有关的物种特异性基因和途径。研究人员还确定了疟疾导致的灵长类基因组变化的特征。研究结果可以促进对灵长类免疫系统如何进化以应对这种宿主-病原体军备竞赛的理解。该分析使用了一种创新方法来调查自然传播系统中的灵长类动物疟疾反应。这项研究可以帮助确定哪些疟疾反应是通过宿主-病原体共同进化军备竞赛产生的，并探索人类和灵长类动物的进化如何受到疟疾选择压力的影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Both humans and non-human primates have evolved defensive adaptations against malaria via changes in the genome. This doctoral dissertation research uses comparative primate data to advance knowledge about the co-evolution of primates and malaria or similar parasites, including how malaria has impacted the evolution of the primate immune system and identification of genetic mechanisms underlying the immune response to blood stage malaria. The project outcomes may inform public health relevant research on the human response to malaria. The project also supports outreach efforts that focus on increasing participation of underrepresented groups in STEM research through K-12 outreach and computational genomic capacity building. Using a comparative functional and evolutionary genomics approach, the researchers identify primate genes and pathways that are differentially expressed in response to malaria infection, including those with species-specific involvement in malaria response. The researchers also identify signatures of malaria-imposed changes across primate genomes. The study outcomes can advance understanding of how the primate immune system has evolved in response to this host-pathogen arms race. The analysis uses an innovative approach to investigate primate malaria response in natural transmission systems. This study can help to determine which malaria responses arose through the host-pathogen coevolutionary arms race as well as explore how human and primate evolution has been impacted by the selection pressure of malaria.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.