Collaborative Research: Adaptive Bridge or Barrier? The Impact of Horizontal Transfer on Genetic Evolution

协作研究：自适应桥梁还是障碍？

• 批准号: 2142720
• 负责人: Brandon Ogbunugafor
• 金额: $ 32.17万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2142720&HistoricalAwards=false
• 关键词: Collaborative; Research; Adaptive; Bridge; Barrier

This award is funded in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Bacteria are an essential part of life on earth, but we do not really understand how they rapidly adapt to new environments. Genes in bacteria are not only inherited from parent to offspring but can also transfer between different species. This “horizontal gene transfer” is often caused by small genetic elements called conjugative plasmids. These plasmids carry the machinery to move copies of themselves into new bacterial cells. A gene on one of these plasmids can inhabit very different host cells over time. A mutation in this gene may then have different effects in each host. This means genes could evolve differently during parent offspring transmission than when they are transferred horizontally between species. This project combines mathematical models and experiments with different bacterial species to measure the effect of horizontal transfer on the evolution of an antibiotic resistance gene and determine how that influences adaptation to changing conditions. Because antibiotic resistance genes are often located on these plasmids, this will aid in combating the evolution of drug resistance. Additional broader impacts include the development of learning tools and a new undergraduate course that will provide authentic research experiences for students. This project has three research aims. First, the researchers will propagate communities with combinations of three bacterial species (Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae) and monitor the evolution of a plasmid-borne gene coding for resistance to beta-lactam antibiotics. Horizontal gene transfer will be manipulated during this process to determine the role of transfer between species in evolution of drug resistance. Second, genetically engineered bacteria will be used to determine why certain mutational sets are favored during horizontal transfer. Mathematically modeling of the results will produce predictions about whether horizontal transfer speeds or hinders the evolution of drug resistance. Third, the researchers will build a computational model to incorporate more realistic features of microbial communities, including more complex environments, migration, and competition between different bacterial species. This model will be tested in live bacterial communities with horizontal transfer turned on or off through plasmid engineering. Overall, this project will elucidate the role that horizontal genetic inheritance plays in the evolution of bacterial communities.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.

该奖项是根据2021年《美国救援计划法》（第117-2）的部分资助。细菌是地球生命的重要组成部分，但我们并不真正了解它们如何迅速适应新环境。细菌中的基因不仅是从父遗传到后代的遗传，而且可以在不同物种之间转移。这种“水平基因转移”通常是由称为偶联质粒的小遗传元素引起的。这些质粒携带机械将其自身的副本移至新细菌细胞中。这些质粒之一上的基因可以随着时间的推移而居住非常不同的宿主细胞。然后，该基因中的突变在每个宿主中可能具有不同的作用。这意味着基因在母体后代传播期间的发展与在物种之间水平转移时的发展相比。该项目将数学模型和实验与不同的细菌物种结合在一起，以测量水平转移对抗生素耐药基因进化的影响，并确定其如何影响对变化条件的适应。由于抗生素耐药性基因通常位于这些质粒上，因此这将有助于对抗耐药性的演变。其他广播公司的影响包括学习工具的开发和新的本科课程，该课程将为学生提供真实的研究经验。该项目具有三个研究目的。首先，研究人员将通过三种细菌种类（大肠杆菌，沙门氏菌和肺炎克雷伯氏菌）的组合传播社区，并监测编码抗β-内酰胺抗生素的抗性的质粒基因的演变。在此过程中，将操纵水平基因转移，以确定物种之间转移在耐药性进化中的作用。其次，基因工程细菌将用于确定为什么在水平转移过程中有利于某些突变集。数学上的结果建模将对水平转移速度或阻碍耐药性的演变产生预测。第三，研究人员将建立一个计算模型，以结合微生物群落的更现实的特征，包括更复杂的环境，迁移和不同细菌之间的竞争。该模型将通过质粒工程打开或关闭水平转移的活细菌群落进行测试。总体而言，该项目将阐明水平遗传遗传在细菌群落进化中所发挥的作用。该奖项反映了NSF的法定任务，并使用基金会的智力优点和更广泛的影响审查标准，被认为是通过评估来获得的支持。