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

Tenenbaum, Debora, Cold Spring Harbor NY

Investigators

Abstract

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.