Please apply to be part of our team! Working in the Brown lab is a fantastic opportunity with great people!
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
Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electro...
www.science.org
The temporospatial distribution of proteins within cilia is regulated by intraflagellar transport (IFT), wherein molecular trains shuttle between the cell body and cilium. Defects in this process impair various signal-transduction pathways and cause ciliopathies. Although K63-linked ubiquitination appears to trigger protein export from cilia, the mechanisms coupling polyubiquitinated proteins to IFT remain unclear. Using a multidisciplinary approach, we demonstrate that a complex of CFAP36, a conserved ciliary protein of previously unknown function, and ARL3, a GTPase involved in ciliary import, binds polyubiquitinated proteins and links them to retrograde IFT trains. CFAP36 uses a coincidence detection mechanism to simultaneously bind two IFT subunits accessible only in retrograde trains. Depleting CFAP36 accumulates K63-linked ubiquitin in cilia and disrupts Hedgehog signaling, a pathway reliant on the retrieval of ubiquitinated receptors. These findings advance our understanding of ubiquitin-mediated protein transport and ciliary homeostasis, and demonstrate how structural changes in IFT trains achieve cargo selectivity. ### Competing Interest Statement The authors have declared no competing interest. Sara Elizabeth O'Brien Trust Postdoctoral Fellowship awarded through the Charles A. King Trust Postdoctoral Research Fellowship Program, , 8460873-01 Richard and Susan Smith Family Foundation, https://ror.org/05j95n956, National Institute of General Medical Sciences (NIGMS), , R01GM141109, R01GM143183