The whole group got together for a summer BBQ, and to celebrate Susan's @dutcherlab.bsky.social election to the NAS 🙌
Great food, better company! 🍻

It’s never easy losing a member of the team. But we’re not saying goodbye, just see you later 😉

@jinghughes.bsky.social you shall be missed! All the best in your new adventure at Yale.

Major congratulations to our fearless leader and team captain Susan Dutcher @dutcherlab.bsky.social for being elected to the National Academy of Sciences! 🙌

Another big win for #cilia biology!!

🚨The new CSH Asia #Cilia and #Centrosome conference program just dropped 👇

World wide reach! WashU and our own Susan Dutcher were featured on the cover of Le Monte (Paris) during Stand Up for Science day.

Major congrats to our team member, Dr. Jennifer Strahle, for being named the Appoline Blair Professor of Neurosurgery! 👏🙌

Check out her lab website for more info on their basic and clinical research programs 👉 www.strahlelab.com

Our group is well represented at the GRC #Cilia & Mucociliary Interactions meeting 💪

David Clapham is visiting WU for the Carl and Gerty Cori Lecture.

Mitochondria are cool, but should’ve really emphasized #cilia 😉

And here's the editor's summary:

11/

We saw that here is an incompetent periciliary barrier in CCDC39/40 variants, increasing susceptibility to injury and infection that is NOT related to ciliary beating, and most likely contributing to the severe lung disease in affected patients.

10/

Finally, we made the startling discovery that loss of CCDC39/40 disrupts the periciliary barrier!

EM analysis showed that the splaying of the axonemal MTs disrupts the cilia membrane and the mucus layer.

9/

scRNA-seq analysis showed an increased number of secretory cells in variant cells.

We discovered that airway epithelia cells in CCDC39/40 variants switch fates to form more secretory cell types in a Notch-dependent manner, consistent with the increased mucus plugging in patients.

8/

Using single cell RNA-seq, we found changes in pathways involved in proteostasis, cell stress, and Notch signaling.

We predict that cellular stress in the variant cells is possibly due to the need to degrade the large burden of undocked ciliary proteins.
7/

We next looked at the order of assembly of the network.

We see there is an orderly assembly sequence, dependent on CCDC39/40 and in the absence of the heterodimer, the proteins remain at the "staging site" for ciliary entry, or are degraded.

6/

Inspection of single particle cryo-EM reconstructions shows that at least 14 of the missing proteins are in direct contact with the CCDC39/40 heterodimer.

Due to this special arrangement, we refer to these 14 proteins as Ciliary Address Recognition Proteins (CARPs).

5/

To determine what was causing this defect in axonemal integrity, we did proteomics of purified cilia from CCDC39 variants.

We found that CCDC39/40 is required for assembly of an elaborate network of >90 ciliary proteins, including the N-DRC, IDAs, RS2 and RS3.

4/

We saw a dramatic loss of ciliary doublet microtubule integrity in human multiciliated cells with CCDC39 and
CCDC40 variants.

The cilia are short, but also are splayed open!

3/

Hello #Bluesky! We'd like to introduce ourselves...

We are the WashU Ciliopathy Research Group - a multidisciplinary team of investigators at Washington University in St Louis that perform fundamental, translational, and clinical research on #ciliopathies.

Follow us for updates from the group! 👇