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Exploring Structure and Function

Scott Bailey Lab

Uncovering the molecular mechanisms that cells use to interact with and modify DNA and RNA, with a focus on CRISPR systems

About the Bailey Lab

Scott Bailey’s lab studies the molecular mechanisms that cells use to interact with and modify DNA and RNA, with a focus on CRISPR systems. Our recent work has provided structural and mechanistic insight into how CRISPR-Cas systems identify and destroy their DNA targets.

Research Overview

Currently, my laboratory focuses on the CRISPR-Cas system, an RNA-based adaptive immune system found in bacteria that protects against invasion by viruses and plasmids. Mechanistic studies of the CRISPR-Cas system are contributing to ongoing efforts aimed at exploiting this system to both protect domesticated bacteria (such as those used in food and pharmaceutical production) and combat human pathogens and the spread of antibiotic resistance. Moreover, RNA-guided nucleases from the CRISPR-Cas system are currently being adapted for genome editing and regulation strategies in a wide variety of organisms, including humans. Indeed, the potential of the CRISPR-Cas toolkit is just being realized and studies centered on understanding how the CRISPR-Cas systems function represents an important need. To this end, my laboratory has provided structural and mechanistic insight into how CRISPR-Cas systems identify and destroy their DNA targets. 

Bailey Lab Research Highlight

CRISPR Spacers: Asymmetry and Orientation

Research led by Bailey Lab PhD student Anita Ramachandran showed that in Escherichia coli, the way that certain exonucleases trim prespacers bound by the Cas1-Cas2 complex results in an asymmetrical prespacer overhangs, helping the system insert the spacers in the correct orientation. The paper, "A moonlighting nuclease puts CRISPR in its place," was selected as a Journal of Biological Chemistry Editor’s Pick Highlight.

Cartoon model of DnaQ cleavage of protospacer: Begins with Cas1-Cas2 bound to a protospacer that has a “TTC” PAM on the bottom strand, and 3’ overhangs on both strands. Next: DnaQ begins cleaving the 3’ overhangs of both strands. Last: DnaQ drops off, top strand overhang is removed, but on bottom strand some overhang remains next to the PAM.

Selected Publications

Ramachandran A, Summerville L, Learn BA, DeBell L, Bailey S. Processing and integration of functionally oriented prespacers in the E. coli CRISPR system depends on bacterial host exonuclease. Journal of Biological Chemistry, 2020.

Singh D, Wang Y, Mallon J, Yang O, Fei J, Poddar A, Ceylan D, Bailey S, Ha T. Mechanisms of improved specificity of engineered Cas9s revealed by single-molecule FRET analysis. Nature Structural & Molecular Biology, 2018.

Estrella MA, Kuo FT, Bailey S. RNA-activated DNA cleavage by the Type III-B CRISPR-Cas effector complex. Genes & Development, 2016.

Mulepati S, Héroux A, Bailey S. Crystal structure of a CRISPR RNA-guided surveillance complex bound to a ssDNA target. Science, 2014.

Chen H, Choi J, Bailey S. Cut site selection by the two nuclease domains of the Cas9 RNA-guided endonuclease. Journal of Biological Chemistry, 2014.

How to Join the Bailey Lab

Bailey Lab members join us from many pathways. Common ways to join the lab are below.

PhD Students

The Bailey Lab is part of several PhD training programs at Johns Hopkins University. Visit the websites below to learn more about the specifics of each program and the admissions process. All programs provide full tuition and stipend support. The Bailey lab usually accepts one PhD student per year, and students typically take six years to complete their degree.

Master's Students

The Bailey Lab hosts students from the Department of Biochemistry and Molecular Biology's Master of Health Science and Master of Science programs. If you are a student in either program and are interested in the Bailey Lab, contact Scott Bailey by email

Undergraduate Students

The Bailey Lab hosts undergraduates from a variety of programs. If you are interested in joining the Bailey Lab as an undergraduate, contact Scott Bailey by email and include your CV, transcript, and one to two paragraphs explaining your interest in the lab. 

Postdoctoral Fellows

To apply to work as a postdoctoral fellow in the Bailey Lab, send a CV along with three letters of reference to Scott Bailey by email. In addition to training within our lab, the Biochemistry and Molecular Biology Department has an active postdoctoral training program.