Max Fels

Hi! Can I be added to the feed please?

orcid.org/0000-0003-14...

I’m grateful to everyone who worked on this project with me–Aidan, Richard, @yoitsjasmine.bsky.social , @molbiolgv.bsky.social , and Chantal. As always, huge thanks to @kranzuschlab.bsky.social and Amy for making it possible for me to work on these kinds of questions!

A model of the function of viral IF4F.

This unique viral replication strategy shows that you can build sophisticated translation regulation through a very simple cap-binding complex. Perhaps there are contexts in which cellular organisms also make use of similar strategies?

But why do these viruses not just rely on the host cap-binding complex? We found that mimivirus replication is unusually resistant to abiotic stresses in a way that depends on viral translation factors. Could it be an adaptation to the unusual stresses faced by the amoeba host?

Crystal structure of viral IF4E bound to a viral cap structure.

How does the viral cap-binding complex specifically promote viral translation? Viral mRNAs carry a unique 5′ UTR motif: a conserved +1A followed by AU-rich sequences. A crystal structure of vIF4E shows exactly how this mRNA cap is recognized!

Transmission electron micrograph showing viral factories in amoebae infected with mimivirus.

This effect becomes obvious when looking at viral factories by TEM. Early in infection these large structures form independent of the viral cap-binding complex, but when this complex is disrupted viral particles cannot assemble.

We call these proteins viral IF4A, IF4E, and IF4G. They 1) form a complex, 2) are essential for viral replication, and 3) act as bona fide translation factors, promoting synthesis of viral structural proteins late in infection.

In amoeba infected by mimivirus, the prototypical giant DNA virus, we found dozens of viral proteins bound to ribosomes—including three that are homologous to the eukaryotic mRNA cap-binding complex (eIF4A, eIF4E, eIF4G).

Transmission electron micrograph of a mimivirus particle.

Giant DNA viruses encode a stunning number of proteins that were long thought unique to living organisms. Among them: translation factors, the master regulators of protein synthesis. But are these viral proteins functional?

Giant DNA viruses encode a hallmark translation initiation complex of eukaryotic life In contrast to living organisms, viruses were long thought to lack protein synthesis machinery and instead depend on host factors to translate viral transcripts. Here, we discover that giant DNA virus...

Are viruses capable of regulating protein synthesis in the nuanced way of cellular organisms? Kinda! I’m excited to share some of my postdoc work that leveraged giant DNA viruses to address this question.

The Panoptes system uses decoy cyclic nucleotides to defend against phage - Nature The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.

Our story describing the Panoptes bacterial immune defense system is now finally peer-reviewed and published today! www.nature.com/articles/s41...

>18,000 new genomes of giant DNA viruses! An incredible trove of new genes and insights into evolution of host-virus interactions from @fmschu.bsky.social and @jgi.doe.gov

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

Congrats! Beautiful work

Nuclease-NTPase systems use shared molecular features to control bacterial anti-phage defense Bacteria encode an enormous diversity of defense systems including restriction-modification and CRISPR-Cas that cleave nucleic acid to protect against phage infection. Bioinformatic analyses demonstra...

Starting the lab Bluesky account to share a preprint from @aragucci.bsky.social and @sadieantine.bsky.social‬ that reveals molecular principles shared across diverse nuclease-NTPase anti-phage defense systems in bacterial immunity (1/7)

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

Shameful. Sorry Jason!

Cool work! Will you add phages or viruses of the rest of eukaryotes?