CAREER: Noise in Gene Expression: How are They Controlled?

职业：基因表达中的噪音：如何控制它们？

• 批准号: 0746796
• 负责人: Jie Xiao
• 金额: $ 61.21万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2014-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0746796&HistoricalAwards=false
• 关键词: CAREER; Noise; Gene; Expression; How

The goal of this CAREER project is to understand how noise in gene expression is controlled. Gene expression, similar to many other biochemical reactions involving small copy number components, is inherently stochastic. Such stochasticity inevitably leads to considerable noise in gene expression. However, "noisy gene expression" is intuitively at odds with the incredible precision cells and organisms achieve during development and growth. How do cells cope with noise, adopting a robust growth pattern while the underlying molecular events are inherently stochastic? In this work, real-time gene expression dynamics in single E. coli cells with unprecedented single molecule sensitivity is followed and the full noise spectrum of gene expression, both the amplitude and frequency, is quantitatively analyzed. Knowledge obtained from this study may bring in the possibilities of designing and building synthetic networks with desired properties to carry out specific functions. The educational component of this project focuses at two levels: K-12 and college. An annual Fun with Science Summer Camp that is freely open to local low-income, underserved students in eight adjacent city elementary schools will be organized to provoke their interest in learning science. At the college level, an elective course Single Molecule Methods will be developed and offered to graduate students in the School of Medicine. The integrated research and education plans allow the PI to expand the participation of underrepresented minority students in scientific research, provide broad training opportunities for high school, undergraduate and graduate students and advance the understanding of the noise control mechanisms in gene expression.

该职业项目的目标是了解如何控制基因表达中的噪音。与许多其他涉及小拷贝数成分的生化反应类似，基因表达本质上是随机的。这种随机性不可避免地导致基因表达中产生相当大的噪音。然而，“嘈杂的基因表达”直观上与细胞和生物体在发育和生长过程中实现的令人难以置信的精确度相矛盾。细胞如何应对噪音，采用稳健的生长模式，而潜在的分子事件本质上是随机的？在这项工作中，以前所未有的单分子灵敏度跟踪单个大肠杆菌细胞中的实时基因表达动态，并对基因表达的完整噪声谱（幅度和频率）进行定量分析。从这项研究中获得的知识可能会带来设计和构建具有所需属性的合成网络以执行特定功能的可能性。该项目的教育部分重点关注两个层面：K-12 和大学。每年一度的“乐趣科学”夏令营将向邻近城市八所小学的当地低收入、服务水平低下的学生免费开放，以激发他们学习科学的兴趣。在大学层面，将开发一门选修课“单分子方法”并提供给医学院的研究生。综合研究和教育计划使 PI 能够扩大代表性不足的少数族裔学生对科学研究的参与，为高中生、本科生和研究生提供广泛的培训机会，并增进对基因表达中噪音控制机制的理解。