Wait. Hold on. The guy who insisted that Sabatini absolutely had to be given a second chance (and offered $25 million in funding) after misconduct allegations and the guy who insisted that Claudine Gay absolutely had to leave after plagiarism allegations - is the same guy? π€¨π€¨π€¨
Some good news at the end of the year: After almost 5 years in the
@NogalesLab
at UC Berkeley, I will move to London in mid-2020 to start my own lab at the
@ICR_London
. A heartfelt "thank you" to all those who supported me along the way.
It's time to properly announce that I have started my own lab at the
@ICR_London
! It's certainly a strange time to start a lab, but I have had wonderful support both from the ICR and from
@NogalesLab
to facilitate the transition. Thank you! New website:
When it comes to the ongoing political crisis in the US,
@sarahkendzior
βs warnings were among the earliest & darkest, but also among the most accurate. The scholar for authoritarian regimes was interviewed by
@AnandWrites
.
My take on high-resolution
#cryoEM
of small complexes has just been published in
@Structure_CP
. In my review, I first introduce how technical developments have enabled
#cryoEM
structure determination of ever smaller targets at better and better resolutions.
Our first "lab paper" is out: In collaboration with Sandro Ataide/Yichen Zhong (University of Sydney) and
@AdrianKoh8
/
@AbhayKot
(TFS),
@JunjieFeng5
determined the structure of the peptide binding domain of SRP68/72, the largest protein components of the eukaryotic SRP.
New
#cryoEM
textbook! Edited by
@NogalesLab
,
@chiulab
and the wonderful Bob Glaeser. Contributions by many experts in the field (too many to list them here).
Some good news before the end of the year: An MRC/UKRI Career Development Award will fund my lab
@ICR_London
for 5 years. Looking forward to more
#cryoEM
of molecular assemblies involved in DNA repair and exciting collaborations! Thanks to all those who made this possible!
New paper: 2.5 Γ -resolution structure of the 85 kDa-CDK/cyclin module of the human CAK in complex with ICEC0942, an inhibitor currently undergoing clinical trials for cancer treatment. Data:
@NogalesLab
, written:
@ICR_London
, collaboration with
@simakali1
.
Our manuscript on the structure of the human CDK-activating kinase has just been made available on
@biorxivpreprint
. Thanks to
@Juanmabertoldi1
, Kif Lim, Tony Iavarone (mass spec), Dan Toso (Berkeley
#cryoEM
) and Eva
@NogalesLab
for their support.
Open post-doc position in my group at
@ICR_London
for mechanistic studies of DNA repair, using
#cryoEM
(of course) and biophysical methods. Long-term aim is to understand structures & mechanisms well enough to target repair pathways using small molecules.
Structure of a pre-60S subunit stuck in the nuclear pore. This is the kind of thing we used to joke about 10 years ago, and we thought it was very (!) funny because ridiculous and completely impossible. Now someone actually did it! Amazing stuff.
#cryoEM
Already one year in London. It has not been the smoothest ride (for obvious reasons), but we are about to get off the ground - with a new lab space suitable for my soon-to-be group of four, funding for 5 years, and lots of work to do. Thanks to everyone for their support.
Too hard to resist the
#ModelAngelo
frenzy. Gave it a go using our small CDK-activating friend. Map computed from 4 hours worth of Glacios 2 data, live processing, 2 hours worth of RELION processing, and then automated modelling without sequence. The quality is quite impressive.
My lab at the
@ICR_London
is recruiting a postdoc interested in uncovering the mechanisms of DNA repair! Candidates with expertise in the biochemistry of nucleic acid/protein complexes or in
#cryoEM
are particularly encouraged to apply. Please have a look!
We're continuing our Glacios 2 Cryo-TEM excitement with a special webinar on Oct. 18 featuring Dr. Basil Greber (
@BJ_Greber
) of
@ICR_London
.
Register to hear how his team used the very first Glacios 2 to facilitate next-gen
#cryoEM
#DrugDiscovery
:
Open postdoctoral position in my lab at the
@ICR_London
to study DNA repair using
#cryoEM
! If you are interested in structural biology and/or biochemistry and molecular biology of DNA repair processes, please have a look (and apply)!
The latest ribosome structure from
@The_Ban_Lab
: The Trypanosome mitochondrial ribosome, by David Ramrath et al. Never seen anything like it: 400 Angstrom diameter, 127 proteins, the largest almost 2000 aa long. Mind-blowing. Congratulations!
Having manually checked 1300 water molecules (and manually built a few 100s), I can still see COOT's blue density mesh when I close my eyes. Yes, that's a good thing.
#cryoEM
Right on time for my arrival at the
@ICR_London
, there's a
@NogalesLab
paper out, with my brand new e-mail address on it: Our paper on the structure of the CDK-activating kinase has been published online in
@PNASNews
. Thanks again to everyone involved!
Some departmental love at my last
@berkeleyMCB
retreat. Thank you to all those who supported me during my stay in Berkeley - and of course special thanks to Eva
@NogalesLab
!
The use of BLUSH for our recent structure has (unsurprisingly) generated considerable interest. I have appended the "how it started" vs. "how it's going" below.
Our first "lab paper" is out: In collaboration with Sandro Ataide/Yichen Zhong (University of Sydney) and
@AdrianKoh8
/
@AbhayKot
(TFS),
@JunjieFeng5
determined the structure of the peptide binding domain of SRP68/72, the largest protein components of the eukaryotic SRP.
New work from our
@ICR_London
neighbours: The lab of
@calfieri84
presents the
#cryoEM
structure of a nucleosome-bound MuvB transcription factor complex, including an approx. 70 kDa module resolved at 3.5 Γ using Glacios/F4 data. Congratulations!
As we go into lockdown once more, looking back on the last 10 years of travel and photography seems to be the best way to appreciate the beauty of our planet and the great outdoors. Stay safe everyone.
This was missed due to major live events happening around the same time, but we have released some of our high-resolution (2 Γ ) and rapid screening
#cryoEM
maps & models of the human CAK bound to small molecules. Paper still under review - more to follow.
Structure validation and peer review still an issue in the
#cryoEM
field. I now routinely ask for maps and models when reviewing and the number of cases that raise concerns is substantial. I often suspect that I was the only reviewer that looked at them.
This is a rather egregious case, and there are many errors in the modelling around the receptor and ligand(s). These errors affect the premise of the paper. How was this not picked up in peer review
@NatureComms
or prior to. Did any reviewers look at the EM maps or model?
Because I encountered an example of a direct interaction in a paper where alphaFold multimer failed to predict any interaction, I was wondering if anyone was doing proteome-wide alphaFold protein-protein interaction screens. Found this - should try:
Behold the amazing phycobilisome, brought to you by
@paulvictorsauer
(
@NogalesLab
),
@TinaDomnguez
(Kerfeld Lab) and colleagues! We have two new pre-prints, one about the PBS structure () and one about its regulation by OCP ().
#CryoEM
Our complete 2.7A structure of a cyanobacterial phycobilisome reveals unexpected conformational changes, the position of the quencher and even a completely new protein! Great collaboration with
@TinaDomnguez
at the Kerfeld lab. Preprints below!
#CryoEM
@UCBerkeley
@LBNLBioSci
Exciting times at
@ICR_London
! Our in-house instrument has been delivered and is being built as we tweet! You may not see it but we have big smiles under our masks. π¬
Looks like a new era of Structural Biology and
#cryoEM
has begun
@ICR_London
: our new Glacios TEM has arrived in its brand-new home, here presented by new Team Leaders
@calfieri84
and
@BJ_Greber
. The future is bright! Thank you to all who made it happen!
Nice! Our CAK-inhibitor
#cryoEM
paper with
@NogalesLab
and
@simakali1
not only graced the cover of
@BiophysJ
but was also named the editor's pick and featured on the journal's blog:
New structural biology conundrum: Do I benefit more from I using my GPU time for improving my
#cryoEM
map using RELION or by predicting the structure of my target using ALPHAFOLD?
Laboratory woes:
Protein: Good job on that purification! I'm doing just fine! Look, I'm swimming in completely clear solution!
Me: Ok, let's load you onto gel filtration. With this nice syringe. I'll be gentle.
Protein: Syringe? Now I am white as milk! LOL! You fool!
Me: π³π
Hallo
@tagesanzeiger
- Sie haben vor kurzer Zeit einen langen Artikel verΓΆffentlicht, in dem basierend auf der Arbeit Klaus StΓΆhrs behauptet wurde, die britische COVID-Variante hΓ€tte keinen Einfluss auf COVID-Fallzahlen. Haben Sie die zu Grunde liegenden Zahlen ΓΌberprΓΌft?
StΓΆhr wird immer dreister mit seinen LΓΌgen und Desinformationen. Das ist wissenschaftliches Fehlverhalten.
Heute behauptet er, der
#B117
-Anteil in UK sei am 15. Januar bei 50% gelegen. Das ist sehr falsch.
Bereits 1 Monat frΓΌher, ca. 15. Dezember war Anteil 50% (s. 3. Grafik) 1/
Crossing this bridge every day on my way to work, this picture started forming in my mind. Yesterday, I finally got around to bringing a camera & tripod to capture it.
#London
#CityScape
captured with
@UKNikon
#NikonZ7
.
Application deadline for this postdoc position in my lab is next Sunday (March 21st). If you are interested in DNA repair and have expertise in structural biology and/or biochemistry of nucleic acid-protein complexes, please have a look at the adβ¬οΈ and our website - and apply. π
Open post-doc position in my group at
@ICR_London
for mechanistic studies of DNA repair, using
#cryoEM
(of course) and biophysical methods. Long-term aim is to understand structures & mechanisms well enough to target repair pathways using small molecules.
Casually dropping the sub-3 Γ
#cryoEM
reconstruction of a 110 kDa-protein in the supplement: "Efficient graphene oxide coating improves cryo-EM sample preparation and data collection from tilted grids." Well done
@avibpatel_
& team!
@NogalesLab
Thrilled to hear that
@Structure_CP
has designated my review on small-complex
#cryoEM
as a featured article in their April issue. If you have not done so yet, have a look here:
My take on high-resolution
#cryoEM
of small complexes has just been published in
@Structure_CP
. In my review, I first introduce how technical developments have enabled
#cryoEM
structure determination of ever smaller targets at better and better resolutions.
Exactly 10 years ago: Our first direct detector adventures
@The_Ban_Lab
. I do not think we had any idea how wild the next decade in
#cryoEM
was going to be.
It may be worth noting that "standard" RELION 4 gave 2.9 Γ resolution, cryoSPARC 3DFlex gave 2.7 Γ (with a larger particle set) and RELION 5/BLUSH gave 3.0 Γ . But the map quality of the latter was clearly the best, and using that map was the obvious choice.
First lab meeting today, and among the things we discussed was
@cushing_v
's recent 1.9 Γ -resolution reconstruction of an inhibitor-bound CAK complex (true 85 kDa - part of MAT1 is deleted). These stunning data were collected by
@AdrianKoh8
and
@AbhayKot
. Thank you!
First attempts at image stacking for night photography: Milky Way, shot at Crater Lake, Oregon.
@NikonUSA
Z7 and 14-24/2.8 @ 14/2.8, 7 frames stacked in Photoshop. Amazed by the performance of the lens and the camera.
@hjf_mueller
Schweizer hier. Habe in meinem Leben nur einmal persΓΆnlich gewΓ€hlt, als ich vergessen hatte, den Briefumschlag rechtzeitig zur Post zu bringen. Bin weder alt noch krank. Wo ist das Problem?
About half of the papers I review do not show the model-map FSC. If you want to know why I will ALWAYS ask for it, no matter how nice your resolution, read the thread below.
#cryoEM
#cryoEM
#structuralbiology
π¬π§ A threadπ§΅...Due to the egregious structural data discussed a few weeks ago I feel there should be a discussion about how we could possibly improve the process in which EM maps and models are validated before deposition. /1
Postdoctoral students and academic researchers at the University of California said they will return to work on Monday after ratifying a new contract. But workers who help teach undergraduates and assign grades remain on strike.
@LugerLab
@nsmb
The people at North Shore Mountain Biking magazine (
@nsmb
) may be disappointed to learn that all that money is not coming their way after all. π
On-grid purification of protein complexes using affinity grids and a 3D printed flow cell. Cool stuff by our London neighbours under Chris Aylett's leadership:
The link to the pre-print is here. Thanks to everyone involved in the project -
@cushing_v
and
@JunjieFeng5
from my lab,
@AdrianKoh8
and
@AbhayKot
from TFS, Kaste Jurgaityte and
@simakali1
from Imperial College, and Ash Bahl from Carrick Therapeutics.
My photographic 2021. London and the Cornwall coast replaced the Californian wilderness and the Nordic outdoors. For now. Shot using
@UKNikon
Z7 & a few nice lenses. π
Some of us keep telling people that
#cryoEM
is easy and everyone can do it and it does not require much skill, and this is the logical result. Who reviews these papers? π΅βπ«
So I bought a 400 mm telephoto and thought I could do some astrophotography with it. Having tried once, I now want an 800 mm telephoto lens. Or a telescope (the below is a 6 MP crop from a 45 MP frame). Why did nobody warn me about the financial risks of getting into astro? π
@hjf_mueller
Wer glaubt, dass es ein Problem ist, wenn eine grΓΆssere Anzahl der Stimmberechtigten von ihrem Stimmrecht gebrauch macht, ist selbst Teil des wirklichen Problems: Voter Suppression.
@NoahShachtman
Seems relevant: "evening curfews to try to stop young people from gathering socially, [...] contributing to the spread [...] most of the contagion that happens within multigenerational homes comes from young people bringing it in." Someone has to bring it into those homes!
The only sane way to deal with the current madness: Camp out atop a mountain, disconnected from the world (and the cell phone signal). But proteins have to be expressed and grant applications have to be written, so I duly returned to work.