Aaron Whiteley

📢Preprint out!
Excited to share my final work from the @soreklab.bsky.social!

We mined phage dark matter using structural features shared by anti-defense proteins (viral tools that help phages bypass bacterial immunity) to guide discovery.

Found 3 new families targeting immune signaling!

Identifying phage proteins that activate the bacterial innate immune system https://www.biorxiv.org/content/10.1101/2025.07.02.662641v1

Two important conceptual advances I want to highlight: using a large library of plasmids expressing 100’s of phage proteins allowed us to (1) identify new phage defense systems independent of genome context and (2) characterize known defense systems that did not yield phage escaper mutants

Our new work understanding how phages are detected by the bacterial immune system is posted on bioRxiv! Check out Toni’s thread for a synopsis👇

Functional amyloid proteins confer defence against predatory bacteria Nature - Escherichia coli uses curli fibres, oligomers of the functional amyloid CsgA, as a barrier to protect against the predatory bacteria Bdellovibrio bacteriovorus and Myxococcus xanthus in a...

A publicly available link for the paper can also be found here: rdcu.be/euu5Y

We are just at the beginning of understanding defense against predatory bacteria and the many roles of amyloid proteins across bacteria. Stay tuned for more great work from the Ledvina lab, starting this year at the University of Michigan!

Great science can only happen with great people. Hannah and all coauthors (including 3 undergraduates!) made this work possible. In particular, our collaboration with Aravind and Max Burroughs at the NIH helped expand this analysis to identify the expanse of bacterial amyloid proteins.

Functional amyloid proteins confer defence against predatory bacteria - Nature Escherichia coli uses curli fibres, oligomers of the functional amyloid CsgA, as a barrier to protect against the predatory bacteria Bdellovibrio bacteriovorus and Myxococcus xanthus in a mechanism th...

Here, we find that defense against predatory bacteria is very different from most modes of defense against phage. Bacteria build a "molecular suit of armor" using functional amyloid proteins to protect themselves. A new role for a fascinating set of proteins. www.nature.com/articles/s41...

I never actually thought my lab would work on Bdello. But, as our work on phage explored the antiviral side of the bacterial immune system we found ourselves thinking that there must also be an antibacterial side too.

"Bdello" is from greek for "to leech" because Bdellovibrio leeches nutrients from other bacteria by growing inside their periplasm! This micrograph from Liz Sockett's review shows the predator in action. www.annualreviews.org/content/jour...

I have been fascinated by predatory bacteria ever since 2013 when I saw a presentation by @markowenmartin.bsky.social on Bdellovibrio bacteriovorus at the West Coast Bacterial Physiologists meeting.

Check out our new study on how bacteria defend themselves against a peculiar clade of organisms – predatory bacteria! This work was a monumental effort led by @hannahledvina.bsky.social (see her excellent summary👇). The bacterial immune system continues to amaze me...

We're thrilled to announce the 2025 class of Jane Coffin Childs Fellows!

See our latest blog post and "look book" to learn more about our newest Fellows and their exciting research!

www.jccfund.org/blog/the-jan...

www.jccfund.org/wp-content/u...

Extremely excited to share I have accepted an offer to be an Assistant Professor in the MCDB department at the University of Michigan! Go Blue! The Ledvina lab will investigate the molecular interworking of the bacterial immune systems including defense against both viral and bacterial pathogens.

DnaJ mediates phage sensing by the bacterial NLR-related protein bNACHT25 Bacteria encode homologs of the human NACHT proteins that form inflammasomes, and use them to defend against phage infection. This study shows that the NLR-related protein bNACHT25 detects diverse pha...

Bacteria encode homologs of the human NACHT proteins that form inflammasomes and use them to defend against phage #infection. @amyconte.bsky.social @aaronwhiteley.bsky.social &co show that bNACHT25 detects diverse phages indirectly through interaction with the host chaperone DnaJ. 🧪
plos.io/4koXP60

Congrats Amy! Here we characterize the sensing mechanism for one of the few defense systems that protects bacteria against RNA phages

A beautiful discovery by Joel Tan and Philip Kranzusch, out today in Nature:

A DNA-gated molecular guard controls bacterial Hailong anti-phage defence

Congrats Joel and Philip! Was a pleasure to contribute to this discovery together with Sarah Melamed

www.nature.com/articles/s41...

Opinion | Trump is killing one of our strongest exports The president wants to balance U.S. trade deficits? He can’t do it without this industry he hates.

Now there's a memorable stat!

"Colleges and universities are among America’s most competitive international exporters. In dollar terms, last year, the United States sold more educational services to the rest of the world than it sold in natural gas and coal combined."

wapo.st/3EvzMCI

Microbial warfare brought us CRISPR. What big breakthroughs could be next? Gene editing and many other useful biotechnology tools came from studies of bacteria fighting off viral invaders. But scientists have only begun to unlock the secrets of this ancient arms race.

Gene editing and many other useful biotechnology tools came from studies of bacteria fighting off viral invaders.

But scientists have only begun to unlock the secrets of this ancient arms race
https://go.nature.com/4lD4LOa

CBASS, CRISPR, and mCpol- oh my! What a satisfying collaboration with @aaronwhiteley.bsky.social 's lab- we uncovered a new cyclic dinucleotide signaling pathway, but it doesn't work how you'd expect! Check out the thread from @aesully98.bsky.social for an overview of the most important findings!

Stop your scrolling and read this AMAZING story from my coworker @aesully98.bsky.social in @aaronwhiteley.bsky.social's lab in collaboration with @benmorehouse.bsky.social ! An immune system which detects anti-immune mechanisms, incredible!!

Thank you to Vince Young for this beautiful highlight of our early work developing an mRNA vaccine for C. difficile (Original paper here: www.science.org/doi/10.1126/...)

A miniature CRISPR-Cas10 enzyme confers immunity by an inverse signaling pathway Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signaling that share mechanistic features with human anti-viral systems[1][1]. In these pathways, including C...

Also check out this contemporary report from @benadler.bsky.social and @erinedoherty.bsky.social in the @doudna-lab.bsky.social! www.biorxiv.org/content/10.1...

A big thanks to our fantastic collaborators at NIH, Aravind and Max Burroughs!

By distributing different variations of Panoptes and CBASS across the bacterial pan genome (aka pan-immune system), bacteria can maintain the upper hand against phages and limit immune evasion.

This creates a dilemma for the virus that is made possible by a key feature of the bacterial immune system–it is distributed across the species. Two strains may have totally different suites of antiphage systems

Here, we report an antiphage system we call “Panoptes” that synthesizes a decoy second messenger. When phage sponge up the decoy, Panoptes acts like a “dead man’s switch”, stopping the phage. The phage must evolve to discriminate between the decoy cyclic nucleotide and the real CBASS nucleotide

One great example of the arms race is how phage absorb nucleotide second messengers using sponge proteins to shutdown bacterial CBASS, an antiphage system related to the human cGAS-STING pathway that relays activation using a cyclic dinucleotide

In the escalating arms race between bacteria and phage, I often wonder how bacteria can keep up. After all, phages replicate more quickly and with greater numbers of progeny

Check out our new story led by @aesully98.bsky.social describing how bacteria turn immune evasion against phage! In collaboration with @benmorehouse.bsky.social lab, we discover that bacteria guard their nucleotide second messenger pool using a nucleotidyltransferase related to Cas10/CRISPR enzymes