Congratulations George

It has been an absolute privilege to be here at Janelia and work on iPALM. Thank you all at AIC for everything. We take back memories to cherish and hope to be back again

Thank you George. It’s a huge responsibility and I look forward to work with you and other editorial board members

Sure, DM

8/9 Thanks to stellar effort from @souravsgw.bsky.social for spearheading this and ably supported by others in the lab as well as superb collaborative efforts from Dr. Jagannath Mondal (TIFR), Prof. Dipshikha Chakravortty (IISc), Prof. Sandip Kaledhonkar and Prof. Roop Mallik (IIT Bombay)

7/9 We also found that host apply this unique defence strategy against variety of pathogens, irrespective of their nature or origin an ability evolutionary inherited from our unicellular ancestors.

6/9 Using a murine sepsis model of Streptococcus pneumoniae infection, we show that p97 limits bacterial proliferation in vivo and protects the host from septic shock, highlighting its crucial role in immune defence.

5/9 Using in-vitro reconstitution, optical traps & electron microscopy, we reveal that p97 uses ATP-driven force to extract bacterial surface proteins, in turn ripping apart the pathogen, releasing their internal contents.

4/9 Our findings reveal four key criteria that dictates p97’s recruitment to bacterial surfaces: (1) Cytosolic exposure, (2) K48-polyUb modification, (3) Presence of ubiquitinable substrates, (4) Recognition by ubiquitin binding cofactors, in this case NPLOC4-UFD1.

3/9 We discovered that host cell unleashes a tweezer-like nanomachine, 🔥VCP/p97🔥, which plucks out these ubiquitinated proteins from bacterial surfaces to disintegrate them and halt infection at its core.

2/9 To tackle the threat, cells tag the surface proteins of these microbes with a death signal: 🚩#Ubiquitin, which marks them for destruction (www.science.org/doi/10.1126/...). But what happens after a pathogen is tagged with ubiquitin?

1/9 We are exposed to countless pathogens every now and then but rarely fall sick. Thanks to our immune system which efficiently disposes them, keeping us safe. But pathogens continuously attack and invade the host cell’s cytosol to gain nutrients and proliferate.

Thank you so much