# Mechanistic Investigation of RNA-Mediated Gene Regulation and Immunity

> **NIH NIH R35** · YALE UNIVERSITY · 2024 · $701,959

## Abstract

Project Summary
The proposed research combines biophysics, molecular genetics, and genomics tools to provide high-resolution
mechanisms for RNA-dominated biological processes. Our study focuses on two central themes in RNA biology.
(1) RNA can serve as an information carrier to guide the action of proteins. Such systems are inherently precise
and programmable, therefore carry great potential in biotechnology and medicine, as exemplified by RNAi and
CRISPR-Cas. My lab spent more than ten years dissecting the mechanisms of CRISPR-Cas, and more recently
has been developing genome editing applications based on our mechanistic insights. (2) RNA can adopt defined
tertiary structures to exert important functions. My lab has elucidated the structure, function, and conformation
dynamics of many riboswitches. The high-resolution information may enable new antibiotics development. We
now aim to combine genetic screen with biochemical purification to systematically identify ligands for orphan
riboswitches. Such studies often reveal novel aspects of bacterial physiology, which may even be conserved in
eukaryotes. We propose to work on the following four areas of research: 1) Structure, mechanism, and genome
editing applications of Type I CRISPR (CRISPR-Cas3); 2) Mechanism of CRISPR immunity establishment by
Cas1-Cas2 integrase; 3) Mechanism and genome editing application of CRISPR-Tn7; 4) Dissecting riboswitch-
controlled mechanism and bacterial physiology.

## Key facts

- **NIH application ID:** 11146928
- **Project number:** 7R35GM118174-09
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** AILONG KE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $701,959
- **Award type:** 7
- **Project period:** 2016-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11146928

## Citation

> US National Institutes of Health, RePORTER application 11146928, Mechanistic Investigation of RNA-Mediated Gene Regulation and Immunity (7R35GM118174-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11146928. Licensed CC0.

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