Doctoral Dissertation Research: Evolutionary Perspectives on Microchimerism

博士论文研究：微嵌合现象的进化观点

• 批准号: 1751388
• 负责人: Daniel Eisenberg
• 金额: $ 3.1万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1751388&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Evolutionary; Perspectives

Beyond conventional genetic inheritance, mothers can impact their offspring's biology through the transfer of immune factors, epigenetic markers, and beneficial microbes. Another lesser-known, non-conventional mode of inheritance is called microchimerism, whereby cells travel between mother and baby during pregnancy, and some colonize and persist for decades after birth. This doctoral dissertation project leverages data from a multigenerational, longitudinal health and nutrition study to investigate microchimerism as a mediating factor in immune tradeoffs throughout the life course. The research aims to better understand how microchimerism may be associated with fetal growth during pregnancy, infant feeding practices, early childhood infectious disease, and pregnancy outcomes in adults. The publicly available data from this longitudinal study and the newly-generated microchimerism data will provide opportunities for student-driven research for undergraduates, including individuals from underrepresented groups.Microchimerism is thought to influence host immune function by directly contributing stem cells that differentiate and develop into functional immune cells and expressing foreign antigens that trigger host immune responses. Most microchimerism research has focused on relationships with autoimmune disorders, cancer, transplant biology, and adverse pregnancy outcomes, leaving considerable gaps in understanding why some individuals are colonized by microchimeric cells more than others, and how these differences might impact evolutionary fitness. To clarify these issues, population-based data from the Cebu Longitudinal Health and Nutrition Survey spanning three generations of participants will be used to investigate the following specific aims: 1) evaluate whether having been breastfed in infancy predicts microchimerism in adulthood, 2) assess whether microchimerism is associated with lower risk of early life infection, and 3) determine whether adult women with microchimerism from their mothers have lower risk of adverse pregnancy outcomes as they have offspring of their own.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.

除了传统的遗传，母亲可以通过转移免疫因子、表观遗传标记和有益微生物来影响后代的生物学。另一种不太为人所知的非传统遗传模式被称为微嵌合体，即细胞在怀孕期间在母亲和婴儿之间旅行，一些细胞在出生后定居并持续数十年。这个博士论文项目利用多代纵向健康和营养研究的数据来研究微嵌合体作为整个生命过程中免疫权衡的中介因素。该研究旨在更好地了解微嵌合体如何与妊娠期间的胎儿生长，婴儿喂养实践，儿童早期传染病和成人妊娠结局相关。这项纵向研究的公开数据和新产生的微嵌合体数据将为本科生提供学生驱动的研究机会，包括来自代表性不足的群体的个体。微嵌合体被认为通过直接促进干细胞分化和发育为功能性免疫细胞并表达引发宿主免疫反应的外源抗原来影响宿主免疫功能。大多数微嵌合体研究都集中在与自身免疫性疾病，癌症，移植生物学和不良妊娠结局的关系上，在理解为什么有些人比其他人更容易被微嵌合体细胞定植以及这些差异如何影响进化适应性方面存在相当大的差距。为了澄清这些问题，宿务纵向健康和营养调查的三代参与者的人口数据将用于调查以下具体目标：1）评估婴儿期母乳喂养是否预示着成年期微嵌合体，2）评估微嵌合体是否与生命早期感染的低风险相关，和3）该奖项反映了NSF的法定使命，并通过使用基金会的智力价值进行评估，被认为值得支持和更广泛的影响审查标准。