NSF RUI: Characterizing Adaptation to Heterogenous and Stressful Environments

NSF RUI：表征对异质和压力环境的适应

• 批准号: 2110494
• 负责人: Karin Kram
• 金额: $ 75.3万
• 依托单位: California State University-Dominguez Hills Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2110494&HistoricalAwards=false
• 关键词: NSF; RUI; Characterizing; Adaptation; Heterogenous

This project takes advantage of experimental evolution in which organisms are evolved in the laboratory under defined conditions. Experimental evolution has been especially successful with microorganisms because they can grow quickly to large population sizes, making the pace of evolution fast enough to study in short periods of time. In this case, the bacteria are propagated under defined but variable environmental conditions to mimic the stressors bacteria encounter in nature. This project aims to characterize the role of gene expression in adaptation and evolution by focusing on the role of genes that can affect cellular behavior by regulating other genes. Mutations in regulatory genes may be particularly advantageous for bacteria in changing environments. This work will be performed in collaboration with undergraduate students at a Hispanic and Minority Serving Institution where almost 90% of students are from groups underrepresented in STEM. Further, the PI will integrate this project into an upper-division microbiology course as an authentic research experience for 48 undergraduate students per year, and perform outreach activities related to this project with K-12 educators. In these ways, the research will help to increase the diversity of students entering the STEM pipeline and leave them better prepared for roles in STEM fields.Changes in gene regulation are a driving force for evolution. Cis regulatory elements are often the cause of evolutionary change when comparing different species, whereas trans regulatory elements are often altered when organisms need to adapt to changing environments. Experimental evolution studies with microbes have begun to probe the role of these factors, but often in unchanging environments where either functional or cis regulatory changes would be favored. The PI will explore the role trans regulatory elements play in adaptation to a heterogeneous environment by first identifying each trans regulatory factor that affects survival of Escherichia coli in long-term cultures in complex media. Then, the PI will characterize the role of these trans regulatory factors in adaptation, by first correlating the genotype with the transcriptome of the population to identify gene expression changes, and determine which of those changes confer the growth phenotype. The PI will then perform experimental evolution on mutant cells to determine how these mutations may change the evolutionary pathways cells can use to adapt to a heterogeneous environment. Understanding how these types of regulatory changes affect adaptation will contribute to the fundamental understanding of evolutionary principles.This research is funded by the Genetic Mechanisms program in the Division of Molecular and Cellular Biosciences in the Directorate of Biological Sciences.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.

该项目利用了实验进化的优势，在实验室中，生物体在规定的条件下进化。 实验进化在微生物方面特别成功，因为它们可以快速生长到大的种群规模，使得进化的速度足够快，可以在短时间内进行研究。在这种情况下，细菌在限定但可变的环境条件下繁殖，以模拟细菌在自然界中遇到的应激源。 该项目旨在通过关注基因的作用来表征基因表达在适应和进化中的作用，这些基因可以通过调节其他基因来影响细胞行为。在变化的环境中，调节基因的突变可能对细菌特别有利。这项工作将与西班牙裔和少数民族服务机构的本科生合作进行，其中近90%的学生来自STEM代表性不足的群体。此外，PI将把这个项目整合到高年级微生物学课程中，作为每年48名本科生的真实研究经验，并与K-12教育工作者开展与这个项目相关的宣传活动。通过这些方式，这项研究将有助于增加进入STEM管道的学生的多样性，并让他们为STEM领域的角色做好更好的准备。基因调控的变化是进化的驱动力。当比较不同物种时，顺式调节元件通常是进化变化的原因，而当生物体需要适应变化的环境时，反式调节元件通常会改变。对微生物的实验进化研究已经开始探索这些因子的作用，但通常是在不变的环境中，功能或顺式调节变化将受到青睐。PI将通过首先确定影响大肠杆菌在复杂培养基中长期培养物中存活的每个反式调节因子，探索反式调节元件在适应异质环境中的作用。然后，PI将表征这些反式调节因子在适应中的作用，首先将基因型与群体的转录组相关联，以鉴定基因表达变化，并确定哪些变化赋予生长表型。然后，PI将对突变细胞进行实验性进化，以确定这些突变如何改变细胞可以用来适应异质环境的进化途径。了解这些类型的调节变化如何影响适应将有助于对进化原理的基本理解。这项研究由生物科学理事会分子和细胞生物科学部的遗传机制计划资助。该奖项反映了NSF的法定使命，并被认为值得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来支持。