Our lab is seeking a Postdoctoral Fellow. The position is intentionally broad, as we are looking for outstanding researchers from diverse scientific backgrounds to advance our understanding of cilia and ciliopathies: academicpositions.harvard.edu/postings/15526
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 β do the eight dynein βrowersβ in #cilia and #flagella operate in the same way?
That makes sense - do you still include the Ub during structure alignment though? As I guess that it should be excluded here and only used for rmsd benchmarking in the next step. For the branched triUb example on github it appears that alignment converged on an attached Ub instead of proximal Ub.
Very nice work! The RMSD of polyubiquitin chains may be biased by strong local alignment on one ubiquitin though, as I can see this happened for the Github example of the branched K11/K48-triUb. In the "no linker" (blue) case the proximal Ub is flipped and K48-Ub landed on K11-Ub and vice versa.
Thanks Leo!
50 day free access with this link ==> urldefense.proofpoint.com/v2/url?u=htt...
Excited to see this work published online at @cp-cell.bsky.social today!
www.cell.com/cell/fulltex...
This work was supported by a postdoctoral fellowship from the Sara Elizabeth O'Brien Trust, the Smith Family foundation, and funding from NIGMS. Last but not least, I would like to thank Alan for his mentorship and support over the last 2 years! @alanbrownhms.bsky.social 8/8
Our multidisciplinary approach, from proteomics to live-cell imaging, shows that CFAP36 is highly conserved across diverse ciliated organisms, pointing to a fundamental role in ciliary biology. π 7/n
Top: Cryo-ET model of the retrograde IFT train (see Lacey et al from Pigino lab) with box around the membrane-facing CFAP36 interaction site. Bottom: Zoomed in view of interaction site and superimposed CFAP36 structure prediction on IFT70 and IFT144.
CFAP36 uses "coincidence detection" to bind two IFT subunits only accessible in retrograde trains β ensuring one-way traffic out of cilia! We validated these interactions in vivo by introducing disruptive mutations in the predicted binding interfaces of CFAP36 and IFT - which stalled CFAP36. 6/n
Plot of ciliary AlphaFold2-multimer screen results ranked by cSPOC score.
How does CFAP36 bind to retrograde IFT trains though? In an unbiased #AlphaFold2-multimer screen using pairwise predictions of ciliary proteins with CFAP36, we identified subunits of both the IFT-A and -B subcomplexes as potential binding partners. 5/n
Live cell #TIRF imaging of flagella revealed that CFAP36 prefers to travel with retrograde IFT trains moving back to the ciliary base. 4/n
Immunofluorescence imaging of murine cilia stained for acetylated tubulin (cilia marker, white) and K63-linked ubiquitin (magenta) in control and CFAP36-depleted cells.
When CFAP36 is depleted in cells, we observed K63-linked ubiquitin accumulating in cilia and disruption of #Hedgehog signaling β a pathway vital for development. This highlights why precise protein export matters for proper signaling. 3/n
Left: Schematic of ciliary IFT machinery transporting cargo up and down cilia. Right: Cartoon of ubiquitinated cargo protein bound to CFAP36-ARL3 adapter complex on retrograde IFT train.
We identified #CFAP36 as a missing link in ciliary protein homeostasis: it connects ubiquitinated proteins to the intraflagellar transport #IFT machinery for removal. But CFAP36 doesnβt act alone: it forms a complex with ARL3, a small GTPase previously known for its role during ciliary import. 2/n
How do cells keep their cilia βcleanβ and functional? Our new study uncovers a conserved mechanism for retrieving polyubiquitinated proteins from #cilia β a process essential for cellular signaling and health. #cellbiology #ciliopathy #ubiquitin #IFT π§΅π 1/n
I am super excited to share our latest work on the structures of doublet microtubules from trypanosomatid parasites, the causative agents of leishmaniasis, Chagas disease, and African sleeping sickness. tinyurl.com/48sh3xn5
Autophagy UK & Proteostasis UK joint meeting -June 3-5. Exploring the lifecycle of cellular components from synthesis to degradation. Going to be a great meeting and we look forward to welcoming you to Dundee! Exciting lineup of speakers and opportunities for ECRs
Register here: tinyurl.com/mr3p49f9
The @alanbrownhms.bsky.social lab is looking for a postdoc to join us at Harvard Medical School #cilia #cryoem #cellbio
jobrxiv.org/job/harvard-...
If you like our visual biochemistry approach at the intersection of transcription and chromatin, consider applying to our lab as a post-doctoral researcher. More info here: farnunglab.com
We are also always looking for Masters students to conduct their thesis research in the Farnung Lab.
Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of @jonmarkert.bsky.social!
tinyurl.com/setd2
As Lorne Protein Meeting approaches its 50th anniversary weβre excited to welcome the fantastic speakers coming in 2025 to celebrate.
www.lorneproteins.org/speakers2025
What can bacteria teach us about ubiquitin? A lot!
In our latest work, Tyler Franklin set out to understand how secreted bacterial ligases catalyze ubiquitin modifications during infection. What he found will surprise you!
www.sciencedirect.com/science/arti...
#CryoEM is addictive! Recognize the warning signs early.
@rcsbpdb.bsky.social has joined Bluesky! Please follow them and post to them. Let's form a strong structural biology community on this site as the bird site continues to descend into...
We're pleased to announce that #RELION5 is now available for beta testing! π₯³π₯³π₯³ Download it for free from github.com/3dem/relion/...
#OpenSoftwareAcceleratesScience
π¦ Minimal Membranes for Minimal Cells π¦ ! In our latest preprint, we introduce an approach to minimize and tune lipidome composition in mycoplasma and the Minimal Cell JCVI-Syn3A. tinyurl.com/53235uzt #Lipidtime @jcvi.bsky.social
I think they come up in the "Life" documentary series narrated by David A. Only learned about them a few weeks ago!
