Joel MJ Tan

Booby traps and viral sponges! Had a really great time with @reneechang.bsky.social distilling our research into a fun 30 sec video describing the arms race between bacteria and viruses. More info at blog.dana-farber.org/insight/2025...

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

08.08.2025 18:40 — 👍 1    🔁 0    💬 0    📌 0

Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

We wrote a review on the free nucleotide pool as a central playground in human, bacterial, and plant immunity – now out in Nature Reviews in Immunology

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

Was fun to write this piece with Dina Hochhauser!

Here is a thread to explain the premises

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30.07.2025 06:05 — 👍 105    🔁 47    💬 2    📌 2

A new preprint led by Sonomi Yamaguchi in our lab describes a bacterial anti-phage defense system named Clover that uses nucleotide signals to both activate and inhibit host immunity.

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

17.07.2025 20:38 — 👍 54    🔁 28    💬 2    📌 3

SAM-AMP lyases in type III CRISPR defence Abstract. Type III CRISPR systems detect non-self RNA and activate the enzymatic Cas10 subunit, which generates nucleotide second messengers for activation

Here we show how the type III signalling molecule SAM-AMP is bound and degraded by a specialised lyase enzyme encoded in cellular and phage genomes. More great work by @haotianchi.bsky.social and the team. @uniofstandrews.bsky.social
academic.oup.com/nar/article/...

14.07.2025 11:07 — 👍 38    🔁 19    💬 1    📌 1

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...

15.07.2025 14:25 — 👍 22    🔁 15    💬 1    📌 1

A DNA-gated molecular guard controls bacterial Hailong anti-phage defence - Nature Animal and bacterial cells use nucleotidyltransferase (NTase) enzymes to respond to viral infection and control major forms of immune signaling including cGAS-STING innate immunity and CBASS anti-phage defence1-4. Here we discover a family of bacterial defence systems, which we name Hailong, that use NTase enzymes to constitutively synthesize DNA signals and guard against phage infection. Hailong protein B (HalB) is an NTase that converts deoxy-ATP into single-stranded DNA oligomers. A series of X-ray crystal structures define a stepwise mechanism of HalB DNA synthesis initiated by a C-terminal tyrosine residue that enables de novo enzymatic priming. We show that HalB DNA signals bind to and repress activation of a partnering Hailong protein A (HalA) effector complex. A 2.0 Å cryo-EM structure of the HalA–DNA complex reveals a membrane protein with a conserved ion channel domain and a unique crown domain that binds the DNA signal and gates activation. Analyzing Hailong defence in vivo, we demonstrate that viral DNA exonucleases required for phage replication trigger release of the primed HalA complex and induce protective host cell growth arrest. Our results explain how inhibitory nucleotide immune signals can serve as molecular guards against phage infection and expand the mechanisms NTase enzymes use to control antiviral immunity.

Nature research paper: A DNA-gated molecular guard controls bacterial Hailong anti-phage defence.

https://go.nature.com/4jXe4GO

01.05.2025 11:37 — 👍 13    🔁 1    💬 0    📌 0

Joel Tan of Dana-Farber Cancer Institute

New research featured in @nature.com from Joel Tan of @danafarbernews.bsky.social’s Kranzusch Lab (kranzuschlab.med.harvard.edu) reports the first example of an inhibitory nucleotide immune signal. Read more: bit.ly/44bz6wW

30.04.2025 16:45 — 👍 3    🔁 2    💬 0    📌 0

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

Excited to share my PhD work in the Kranzusch Lab published in @nature.com!

Two key discoveries:
- Nucleotides can act as negative regulators of antiviral immunity
- Ion channel activation is gated by DNA

Thank you to our all collaborators! @soreklab.bsky.social

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

30.04.2025 18:57 — 👍 62    🔁 18    💬 2    📌 1