Kevin Forsberg
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kvnforsberg.bsky.social
Kevin Forsberg
@kvnforsberg.bsky.social
Assistant Professor, Department of Microbiology, UT Southwestern. Posts are my own.

Lab Website: forsberglab.org
Banner Art: Tamanash Bhattacharya
We also find a whole slew of new phage defenses – outer membrane proteins, abortive infection, and genes without sequence or structural homology to any known protein. If you have the time (and mental energy), consider giving our preprint a look and telling us what you think!

8/10
March 3, 2025 at 12:12 PM
We cloned and purified one of these nucleases and – yep! – it could degrade genomic DNA from both Mu and T4. In fact, its nuclease activity against these DNA substrates in vitro correlated roughly with its phage defense activity in vivo.

7/10
March 3, 2025 at 12:12 PM
Homologs of the nuclease PD-T4-3 were our most common defense gene (first identified by Vassallo and Laub, *hat-tip*). These genes defended against T-even phages and phage Mu. This is surprising b/c T-even phages and phage Mu modify entirely different nucleotides with wildly different marks.

6/10
March 3, 2025 at 12:12 PM
Why do we say this? Because a mutant phage without these modifications is resistant to many of these nuclease defense systems. We purified a few nucleases and confirmed, yes, that’s what happening here!

5/10
March 3, 2025 at 12:12 PM
Nucleases are particularly common – implying that these defenses cross phylogenetic boundaries exceptionally well. Many of these nucleases likely recognize covalent modifications on phage DNA to activate restriction.

4/10
March 3, 2025 at 12:12 PM
A lot!

We found >200 defense inserts from 63 selections, from every habitat surveyed and against each phage tested. These DNA inserts come from 14 different phyla yet function in E. coli against its phages. Cross-compatibility across huge evolutionary distances!

3/10
March 3, 2025 at 12:12 PM
My lab’s first preprint!

We used functional metagenomics to identify phage defenses in human and soil microbiomes. We scaled these selections while maintaining accuracy, enabling us to examine 9 habitats for defense elements against 7 phages.

www.biorxiv.org/content/10.1...

1/10
March 3, 2025 at 12:12 PM