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

这个CAREER项目的目标是了解基因表达中的噪音是如何被控制的。基因表达，类似于许多其他涉及小拷贝数组分的生化反应，具有固有的随机性。这种随机性不可避免地导致基因表达中存在相当大的噪声。然而，“嘈杂的基因表达”在直觉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不一致。细胞如何应对噪声，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了单个大肠杆菌细胞中的实时基因表达动态，并定量分析了基因表达的全噪声谱，包括振幅和频率。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实现特定功能的可能性。这个项目的教育部分集中在两个层面：K-12和大学。为了激发学生们学习科学的兴趣，将在邻近的8所城市小学免费举办每年一次的“科学乐趣夏令营”。在大学阶段，将为医学院的研究生开设一门选修课程“单分子方法”。综合研究和教育计划使PI能够扩大代表性不足的少数民族学生参与科学研究，为高中生，本科生和研究生提供广泛的培训机会，并促进对基因表达中噪声控制机制的理解。

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.