Doctoral Dissertation Improvement Grant: Gene Loss During Catarrhine Evolution With Possible Implications for the Evolution of Resistance to Viral Infections

博士论文改进补助金：卡他碱进化过程中的基因丢失对病毒感染抵抗力的进化可能产生影响

• 批准号: 0925717
• 负责人: Laurie Godfrey
• 金额: $ 1.5万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0925717&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Grant; Gene

Certain pathogens, including viruses, appear to utilize the alpha1-3GT gene, its enzymatic pathway, or its product gal-alpha1-3Gal in their infection cycles. This study investigates how the alpha1-3GT gene and its product, gal-alpha1-3Gal (present on host cells), affect viral infectivity in primates. Among mammals, catarrhines (Old World monkeys and apes) are the only ones that do not express the alpha1-3GT gene which was inactivated ~28 million years ago. If it can be established that these pathogens do indeed use the gene, its enzymatic pathway, or its product, in their infection cycles, then the selective advantage of this gene inactivation becomes clear. To test this possibility, experiments will probe the mechanisms by which viruses can (or cannot) utilize the gene or gene product. In vitro experiments on parallel mouse and primate cell lines, genetically modified to express the alpha1-3GT gene, will test the differential infectivity of viruses. Additionally, genetically modified mouse lines, one expressing the alpha1-3GT gene and the other with the gene "knockedout" will be used to corroborate in vitro work and to test pathogenesis.This research elucidates how different viruses use glycosylation pathways or carbohydrates as binding sites or receptors. This has biomedical implications by contributing to understanding how the immune system responses to infection. It also elucidates variation in viral virulence in catarrhines and other species including its contribution to selective pressures and species survival. The broader impacts of this study include primate conservation, as conservation biologists are increasingly aware of the threat of emerging diseases in primate communities. Understanding which viruses are likely to be most dangerous to particular hosts may be critical in making informed policy decisions. This doctoral dissertation research project will contribute to the academic training of a female graduate student who is a member of the American Hispanic community. This research will broaden her ability to contribute to the growing discipline of global disease ecology.

某些病原体，包括病毒，似乎在其感染周期中利用α 1 -3GT基因、其酶促途径或其产物gal-α 1 -3Gal。 本研究调查了α 1 -3GT基因及其产物gal-alpha 1 -3Gal（存在于宿主细胞上）如何影响灵长类动物中的病毒感染性。 在哺乳动物中，卡他类动物（旧大陆的猴子和猿）是唯一不表达α 1 -3GT基因的动物，该基因在2800万年前失活。 如果能够确定这些病原体在其感染周期中确实使用了该基因、其酶促途径或其产物，那么这种基因失活的选择性优势就变得清晰了。 为了验证这种可能性，实验将探索病毒能够（或不能）利用基因或基因产物的机制。 对平行的小鼠和灵长类动物细胞系进行的体外实验将测试病毒的差异感染性，这些细胞系经过遗传修饰以表达α 1 -3GT基因。 此外，转基因小鼠品系，一个表达α 1 -3GT基因，另一个与基因“敲除”将被用来证实在体外工作和测试pathogenicity.This研究阐明不同的病毒如何使用糖基化途径或碳水化合物作为结合位点或受体。 这有助于理解免疫系统如何对感染做出反应，从而具有生物医学意义。它还阐明了在卡他鼻和其他物种，包括其选择压力和物种生存的贡献病毒毒力的变化。 这项研究的更广泛影响包括灵长类动物保护，因为保护生物学家越来越意识到灵长类动物社区中新出现的疾病的威胁。 了解哪些病毒可能对特定宿主最危险，对于做出明智的政策决定至关重要。 这个博士论文研究项目将有助于一个女研究生谁是美国西班牙裔社区的成员的学术培训。这项研究将扩大她的能力，为全球疾病生态学的不断发展做出贡献。