# Defining mechanisms of diverse CRISPR-Cas complexes

> **NIH NIH R35** · IOWA STATE UNIVERSITY · 2021 · $386,997

## Abstract

PROJECT SUMMARY/ABSTRACT
 Bacterial populations, including those that affect human health, are largely controlled by
bacteriophages. Phages change the composition of bacterial ecosystems and strongly influence
bacterial evolution. Defense mechanisms that protect bacteria from phages are important
regulators of these host-pathogen interactions. Defining these mechanisms is crucial to
understanding bacterial compositional dynamics and pathogenicity. CRISPR-Cas systems are
sophisticated and diverse mechanisms that allow bacteria to memorize infection events and
defend themselves upon reinfection. In addition to their important role in mediating bacteria-
phage interactions, CRISPR-Cas systems have been harnessed for genome manipulation
technologies that have greatly facilitated biomedical research and have enormous potential for
human therapies. The goal of our research program is to fully define the mechanisms and
specificities of a variety of nucleic acid-protein complexes that direct CRISPR-mediated
immunity and have potential for CRISPR technology. Our program is divided between
understanding the process of adaptation, during which a bacterial cell is immunized, and
interference, during which the CRISPR-Cas system neutralizes an infection. We and others
have recently discovered higher-order adaptation complexes containing poorly defined protein
subunits that are essential for effective immunization. Our goal is to uncover the molecular steps
that enable specificity and precision by higher-order adaptation complexes, ensuring productive
immunization events. Following immunization, Cas effector complexes that neutralize infection
during interference must quickly recognize pathogens, a task made even more challenging
when phages evolve and evade detection. Our goal is to understand how Cas effectors can
maintain effective immunity even in the face of pathogen evolution. Through this research
program, we will contribute to the overall understanding of how CRISPR-Cas systems impact
bacterial populations and help ensure that CRISPR-based research and therapeutic tools are
used safely and effectively.

## Key facts

- **NIH application ID:** 10167340
- **Project number:** 1R35GM140876-01
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Dipali Gurudutt Sashital
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,997
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167340

## Citation

> US National Institutes of Health, RePORTER application 10167340, Defining mechanisms of diverse CRISPR-Cas complexes (1R35GM140876-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10167340. Licensed CC0.

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