This was a wonderful collaboration with Sophia Fochler, Eva Gluenz, @zephyris-science.bsky.social, @alanbrownhms.bsky.social, and more analyzing a mountain of data. We are also grateful for the support through a dual NSF and Swiss NSF grant.
Want to know more without the sports analogy? Check out the full story on bioRxiv www.biorxiv.org/content/10.1...
We also knocked out individual doublet microtubule subunits, revealing which structural elements are important for movement. Together, our work provides a new framework for understanding how diverse molecular “rowers” coordinate ciliary motility.
Next, we systematically deleted each dynein gene and analyzed how these knockouts altered flagellar movement. The results were surprising: each dynein distinctly impacted motility, but not necessarily in the ways predicted from earlier studies.
Using Leishmania as a model, we determined the cryo-EM structure of the doublet microtubule to pinpoint the position of each dynein. This gave us a detailed map of where every “rower” sits on the ciliary “boat.”
In an eight-person rowing boat, each rower contributes to movement but also has a unique role: balancing, powering, or setting the rhythm and pace. In our latest collaborative work we asked – do the eight dynein “rowers” in #cilia and #flagella operate in the same way?
Excited to share our new @science.org paper! Led by postdocs Ruchao Peng and Xin Xu, we used cryo-EM/ET to reveal the influenza ribonucleoprotein complex structure and its strand-sliding mechanism for RNA synthesis, paving the way for new antivirals.
www.science.org/doi/10.1126/...
How do cells keep their cilia “clean” and functional? Our new study uncovers a conserved mechanism for retrieving polyubiquitinated proteins from #cilia – a process essential for cellular signaling and health. #cellbiology #ciliopathy #ubiquitin #IFT 🧵👇 1/n
Finally this work wouldn’t be possible without the team
in the Brown lab @alanbrownhms.bsky.social
This was a fantastic collaboration with @ruizhangmt.bsky.social, Richard Wheeler, and Eva Gluenz. Check out the paper for more!
It is also important to highlight that this work was made possible by funding through multiple NIH and NSF grants. These funding mechanisms are vital for biomedical research.
Our strategy of combining structural analysis with comprehensive genetic knockout, promises to continue uncover the mechanisms that control flagella-based motility.
We also observe trypanosomatid-specific axoneme specializations. One example is the B-tubule ponticulus structure, which was first observed nearly 60 years ago! We find that the lumen-spanning structure is made up of three components, whose periodicity is established by a filamentous MIP.
Using CRISPR, we knocked out each of our identified proteins and tested the mutant swimming speed. Our analysis found that the doublet is surprisingly resilient to individual MIP knockout. However, we show that the evolutionarily conserved inner junction is uniquely sensitive to knockout.
Our structure revealed a highly specialized doublet containing 51 microtubule inner proteins (MIPs). Once resolved, we used Leishmania as a model to test the contribution of each MIP to motility.
