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

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。人类和非人类灵长类动物都通过基因组的变化进化出了抵御疟疾的防御适应能力。这项博士论文研究使用比较的灵长类数据来促进关于灵长类和疟疾或类似寄生虫的共同进化的知识，包括疟疾如何影响灵长类免疫系统的进化，以及识别对血期疟疾免疫反应的遗传机制。该项目的成果可能为有关人类对疟疾反应的公共卫生相关研究提供信息。该项目还支持外联工作，重点是通过K-12外联和计算基因组能力建设，增加代表不足的群体对STEM研究的参与。利用比较功能和进化基因组学方法，研究人员确定了应对疟疾感染时差异表达的灵长类基因和途径，包括那些参与疟疾反应的物种特异性基因和途径。研究人员还确定了灵长类动物基因组中疟疾造成的变化的特征。这项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。这项分析使用了一种创新的方法来研究灵长类疟疾在自然传播系统中的反应。这项研究有助于确定通过宿主-病原体共同进化的军备竞赛产生了哪些疟疾反应，并探索人类和灵长类动物的进化如何受到疟疾的选择压力的影响。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.