Jack Dunkle
University of Alabama, AL·Biochemistry
Bacteria and archaea defend themselves against viruses and other invading genetic material using CRISPR-Cas systems, molecular machines that carry a short guide RNA and use it to find and destroy matching foreign DNA or RNA. A key open question is how these machines tell a true target from a near-match, since mistakes could mean attacking the cell's own genes.
- Fields
Biochemistry
Microbiology & Immunology
Biophysics
- Topics
Cas10
Csm complex
Type III-A CRISPR-Cas
- Grants
- 1 known grant, through Jun 2027
What they work on
- Test whether mismatches at specific sensitive positions in the guide RNA-target RNA duplex shut down interference by the Cas10-Csm complex, defining the accuracy rules for RNA-targeting Type III CRISPR-Cas systems.
- Test whether Csm2, a subunit predicted to contact the bound target RNA directly, senses correct target binding and relays that signal to the Cas10 enzyme through structural change.
- Determine the structural mechanism of Cas10 activation using cryo-electron microscopy, imaging the roughly 300-kDa Cas10-Csm complex in target-free and target-bound states.
- Combine biochemistry and biophysics to measure how DNA- and RNA-degrading activities of Cas10-Csm are triggered and regulated once foreign RNA is detected.
More about the research
Much is known about how the DNA-cutting systems (Cascade and Cas9) achieve this accuracy, but far less is known about the systems that recognize single-stranded RNA instead.
Why it matters
Type III-A CRISPR-Cas systems shape how mobile genetic elements move between bacteria, a common route by which antibiotic resistance genes spread, so a clearer mechanistic picture could inform efforts to limit that spread. Because these systems detect RNA, understanding what makes them accurate could also support their use as point-of-care diagnostics for RNA viruses.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Scott Bailey
Johns Hopkins University, MD·Biochemistry
Determine how CRISPR-associated proteins use small guide RNAs to locate and destroy foreign DNA or RNA in prokaryotes, using cryo-EM structures together with biochemical, biophysical and cell-based assays.
Andrew Santiago-Frangos
University of Pennsylvania, PA·Biochemistry·Early-career
Find conserved DNA motifs in CRISPR leader sequences that may control spacer integration, transcription or RNA processing, using a bioinformatic search across CRISPR systems.
Rick Russell
University of Texas at Austin, TX·Biochemistry
Measure how mismatches between guide RNA and target weaken CRISPR-Cas binding, testing whether the penalty is predictable from the properties of the R-loop or RNA helix.
The school
University of Alabama: 22 labs on PI Pages, $221M a year on research, 235 research doctorates a year.
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