# Defining the ligandability of bacterial RNAs

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $66,390

## Abstract

PROJECT SUMMARY
Most bioactive small molecules function by targeting proteins. Complex RNA structures are, in principle,
also targetable with small molecules. However, apart from bacterial riboswitches, natural products that
bind a small number of sites in the ribosome, and a handful of human-designed ligands, we know very
little of the capacity of small molecules to bind RNA or to modulate RNA function. During the first year of
my postdoctoral training, I demonstrated the feasibility of a new technology, called Frag-JuMP, that
simultaneously identifies RNA-binding ligands and maps RNA-ligand binding sites at nucleotide resolution.
The current version of the technology requires gene-specific primers. Therefore, one goal of this project is
to develop a generic approach for examining the ligand-binding ability of large RNAs. A second goal is to
use Frag-JuMP to interrogate ligand-binding by the bacterial ribosomal RNA in live cells to understand
fundamental principles that allow ligands to bind selectively to complex RNAs and to identify RNA-ligand
binding sites in functional regions of the ribosome. These studies are expected to characterize RNA
structures capable of binding small molecules and to identify the subset of these that constitute ligand-
binding sites likely to modulate ribosome function. The long-term, sustained impacts of this research and
training project include the creation of a comprehensive RNA-ligand discovery strategy that can
immediately be used to discover RNA-binding molecules and to provide an unprecedented picture of
ligand-binding sites in any cellular RNA. Molecules identified by Frag-JuMP are also readily linkable,
facilitating generation of potent bivalent ligands by linking co-binding fragments. The field of small-
molecule, RNA-targeted therapeutics is in its infancy and represents an enormous opportunity to
manipulate the functions of diverse cellular processes in bacterial and eukaryotic cells. Training will
emphasize development of new expertise in RNA chemical probing methods, technologies based on high-
throughput sequencing, bioinformatics analyses, cell culture methods, and small-molecule fragment
chemistry. This training, combined with my previously developed expertise in chemical synthesis, will
equip me with unique, career transforming, skills in chemical biology and structural genomics. Upon
completion of this cross-disciplinary training program, I will be equipped for a leadership position at the
interface of chemistry and biology, focused on understanding how RNA structure governs biological
mechanism and on developing RNA-targeted therapeutics.

## Key facts

- **NIH application ID:** 10315245
- **Project number:** 1F32GM143863-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jordan T Koehn
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315245

## Citation

> US National Institutes of Health, RePORTER application 10315245, Defining the ligandability of bacterial RNAs (1F32GM143863-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10315245. Licensed CC0.

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