NSF Postdoctoral Fellowship in Biology: Defining and programming transcriptional activatability in bacterial promoters

该行动资助了美国国家科学基金会2023财年生物学博士后研究奖学金，扩大生物学中代表性不足群体的参与。为了生存，细胞需要在不同的时间开启和关闭不同的基因。一个基因何时以及有多强被激活取决于它之前的DNA序列，以及与该DNA序列结合并控制基因活性的不同调节蛋白。该项目旨在了解DNA序列如何控制细菌中的基因活性，并使DNA序列的设计具有可预测的激活和可预测的对调节蛋白的敏感性。通过在现代基因组学和人工智能技术方面的培训，该奖学金将为不同生物系统中基因调控的定量机制研究建立框架。为了扩大生物学中代表性不足的群体的代表性，该研究员将为拉丁裔博士后建立一个虚拟社区。细菌中基因表达的大部分调控发生在转录起始阶段。为了启动转录，RNA聚合酶通过多个动力学步骤，其速率被编码在基因组DNA中。然而，很少知道动力学这些不同的步骤是如何由启动子DNA序列编程。本研究旨在量化整个大肠杆菌基因组中数千个启动子的转录起始各个步骤的动力学，量化转录因子对转录起始动力学的启动子特异性作用，并定量定义转录起始动力学由DNA序列编程的方式。研究目标将通过将基于高通量测序的实验技术与贝叶斯推理策略和深度学习方法相结合来实现。同时，该研究员将为拉丁裔博士后建立一个虚拟社区，为成员提供资源和支持网络，从而帮助扩大在生物学中代表性不足的拉丁裔社区的代表性。该奖项反映了美国国家科学基金会的法定使命，并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，被认为值得支持。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2023, Broadening Participation of Groups Underrepresented in Biology. In order to survive, cells need to turn different genes on and off at different times. When and how strongly a gene is turned on depends on the DNA sequence preceding it and on different regulatory proteins that bind to that DNA sequence and control gene activity. The project seeks to understand how the DNA sequence controls gene activity in bacteria and to enable the design of DNA sequences with predictable activation and predictable sensitivity to regulatory proteins. By training the fellow in modern Genomics and Artificial Intelligence techniques, the fellowship will establish a framework for quantitative mechanistic studies of gene regulation in diverse biological systems. To broaden the representation of underrepresented groups in Biology, the fellow will establish a virtual community for Latinx postdocs.Most regulation of gene expression in bacteria occurs during transcription initiation. To initiate transcription, RNA polymerase traverses through multiple kinetic steps, the rates of which are encoded in genomic DNA. However, little is known about how the kinetics of these distinct steps are programmed by promoter DNA sequence. The research aims to quantify the kinetics of individual steps in transcription initiation for thousands of promoters throughout the E. coli genome, quantify the promoter-specific effects of transcription factors on transcription initiation kinetics, and quantitatively define the ways in which transcription initiation kinetics are programmed by DNA sequence. The research aims will be achieved by combining experimental techniques based on high-throughput sequencing with Bayesian inference strategies and Deep Learning methods. In parallel, the fellow will establish a virtual community for Latinx postdocs that will provide members with resources and support networks, thereby helping to broaden the representation of the underrepresented Latinx community in Biology.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.