Congrats to our grad students who pitched therapeutic targets at this year's @ScrippsGradPrgm Drug Discovery Shark Tank - particularly Shelby @ShelbyFerrier and Morgan @m_m_gee on their winning proposal to target Cholera toxin subunit B, which raised $4 million!
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The human mitochondrial ClpXP is uniquely assembled and regulated compared to its bacterial counterparts. Congrats to Kelly Chen on her years of hard work on this challenging complex! biorxiv.org/content/10.1101/…
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Proof our lab skills are cutting-edge—both at the microscope and the (pumpkin carving) bench! 🎃🔬 #CryoEM #PumpkinScience @scrippsresearch
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Some thoughts on the current state of single particle cryo-EM map/model validation. (TLDR: preferred orientation remains a big problem, ❤️ Q-scores. There's been progress, but there's still more to do. ) authors.elsevier.com/sd/arti…
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We always thought nucleotide state strictly defined AAA+ conformation, but Jeff Mindrebo's work on mito LONP1 suggests more is at play - substrate interactions also drive protein translocation! Revisiting & rethinking the hand-over-hand mechanism: tinyurl.com/49y7a6h6
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Our first foray into the fascinating field of DNA repair! Congrats to postdoc Chris Zerio @chriszerio, who tested hundreds of oligos to identify one that trapped the helicase of human Polymerase θ in the process of annealing two strands of DNA. tinyurl.com/jaddar9u
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Congrats to all the participants of the 2024 @cshlcourses cryoEM course, and special congrats to Team 3: @Nancy_Jaiswal23, @Denjoi1, Edem Gavor, the winners of this year’s competition! We hope you all had a great time and share the knowledge you’ve gained with others!
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Kicking off the 2024 Cold Spring Harbor CryoEM course @cshlcourses! It’s going to be a grueling but amazing 2 weeks!
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Further evidence of high-resolution capabilities at 100 keV with a side-entry cryo holder using the @GatanMicroscopy Alpine detector. It even performed better than the K3 on a small sample - Great collab with colleagues in Verba lab @UCSF biorxiv.org/cgi/content/shor…
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Symmetric transthyretin (55 kDa) has been crystallized hundreds of times - why look at it by cryoEM? Good thing @BenjaminBsnt did! Asymmetry, distinct binding pockets, multiple conformations - explains negative cooperativity & amyloidogenic pathway: tinyurl.com/yf67muvv
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Blown away to have received the Mentor of the Year award @scrippsresearch . So grateful for the incredible support from everyone involved. Your dedication to science is my greatest reward. Thank you for making every day so inspiring 🙏
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1) Remove the silly acrylic box
2) move to a cold room and bring a humidifier (or hang some wet towels)
3) blot from the front and reproducibly get great vitreous ice (with a bit of practice), as shown by Mark Herzik below. See also herziklab.com/manual-plunge.…
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Heard whispering from the twins’ room at 5:30 this morning. They were working to fix a down (Lego) Glacios microscope. Dedicated service engineers! @thermosciEMSpec
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Congrats to Alex Salazar @alexxsaladbar on passing her candidacy exam today! Always one to innovate, Alex opted to celebrate with LN2 “blue”-flavored raspados in lieu of traditional LN2 ice cream. They were delicioso!
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Mitochondrial stress causes DELE1 to form a large signaling scaffold that activates the integrated stress response. Congrats @_JieYang for initiating this project several years ago, and our amazing collaborators in the @LabWiseman and @KampmannLab labs! rdcu.be/diKmx
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Diversity in science not only brings unique perspectives & experiences that drive innovation and enrich our research - it also gives us the opportunity to taste delicious dishes from around the world! Lab potluck with amazing food from more than 10 countries!
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Congrats to twitterless Kelly Chen for accomplishing a major step towards completing her PhD! And for concocting a killer Vietnamese Coffee LN2 ice cream recipe!
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lower energy e- more readily interact with sample, increasing radiation damage (see image from Peet et al. 2019, 4 Å resolution disappears faster at 100 keV than 300). But Russo and colleagues argue that you get more signal per unit of damage at 100 keV: journals.iucr.org/m/issues/2…
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Been so long since we’ve done this! Chocolate brownie LN2 ice cream to celebrate Lauren @lalexandrescu1’s PhD candidacy!
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Congrats to all the participants, TAs, lecturers, and co-instructors of the 2023 @CSHL #cryoEM course! Special congrats to Group 4, winners of this year’s competition: @ebruguera, @Nele80833806, and @YukiOA94!!!
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Data collection competition at the @CSHL #cryoEM course! Teams are trying to find the best ice for high resolution @CharlCrowe @kayla_m_perry_ @FirasFadel_BZ
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Four course instructors trying to make graphene oxide grids for the first time at 11pm for tomorrow’s demo at the @CSHL #cryoem course. What could possibly go wrong? @Jen_Cash_11 @kollmanlab
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Looking for a postdoc to take on cryoEM studies exploring how small molecules impact E3 ligase conformation and substrate binding (a la science.org/doi/10.1126/scie…). Send an email w/ CV to glander@scripps.edu
please retweet
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Thank you students, TAs, lecturers, and instructors for making the @CSHL CryoEM course so enjoyable. Looking forward to the next course in March!
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Finally able to kick off the @CSHL cryoEM course originally scheduled for March 2020! It’s great to be back
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With a heavy heart I announce the loss of the Scripps Morgagni. With over 20 years of faithfully mediocre imaging, it is now at peace after a year-long battle with HT issues. RIP
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Join us TODAY for Mia Shin @_miashin's thesis defense, entitled "A Tale of Two Lons: Mechanistic insights on the AAA+ Protease Lon from Bacteria and Humans" (Monday, Feb 22 at 2PM PST) scripps.zoom.us/j/9277644939…
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The anti-CRISPR AcrIF9 mounts a two-pronged attack against the Csy #CRISPR system: 1) the usual approach (blocking target DNA binding), 2) making CRISPR complexes bind non-specific DNA. Congrats to @marschahirschi & our collaborators in the Wiedenheft lab! rdcu.be/b4ycq
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Wow! Cold FEG + Falcon 4 + RELION = 1.22 Å of apoferritin. Great for #CFAR, but what's more impressive is the reconstruction of β3 GABAA receptor with regions resolved to ~1.6 Å! Congrats @SjorsScheres & colleagues! What a day for the #cryoEM community biorxiv.org/content/10.1101/…
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We'd put an exclamation mark in the title as well! Really impressive work from the Stark group - single particle #cryoEM closing in on 1 Å resolution! (and so happy we can finally tweet about it @HaselbachLab 😉) biorxiv.org/content/10.1101/…
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The movies and figures associated with this publication are another example of why #WeNeedChimeraX! Here's a movie showing how the proteolytic active sites of Lon are activated upon substrate binding. @UCSFChimeraX
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The Lon protease undergoes a stunning rearrangement when it degrades proteins - this movie summarizes how we think these #ProteinGymnastics proceed. Congrats @miashin & @puchadesEM, another fun collab w/ Karzai lab and @LabWiseman! advances.sciencemag.org/cont…
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Congrats to @albertssong on passing his candidacy exam! Now we just have to work on his liquid N2 ice cream-making skills...
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Outstanding evening at #bps2020, great lineup of speakers at the #cryoEM subgroup (thanks to organizers @TheVillaLab, @Mel_Ohi_lab, and @kellogg_liz!) and then catching up with the CryoEM “boomers” afterwards!
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Many many thanks to @moriya_toshio, @RadoDanev, & @mkikkawa for showing me around KEK @kek_jp & the University of Tokyo @UTokyo_News_en! I had an awesome time and learned so much - and I saw so many big, expensive toys!! So excited for the future of #CryoEM in Japan!
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Sometimes programs need help finding your target of interest in noisy subtomograms. Although it works astonishingly well, this method is NOT high throughput & requires loads of elbow grease (see attached photo of the guided approach in action!) @nani_grotjahn @saikatLab
A guided approach for subtomogram averaging of challenging macromolecular assemblies biorxiv.org/cgi/content/shor…
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Yes! We’ll hold the resolution record for single particle CryoEM until the reported resolution is updated to the correct value on Wednesday! #thisIsEmbarrassing
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Don't forget to add some custom cardboard roofing to minimize sample drift when it's done. @WimJHH might be able to help you out with this (attaching an image of his beautiful handiwork on an Arctica)
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"Assuming good biochemical preparation and rapid freezing, there are only TWO reasons that cryo-grid preparation can fail:
1) Interaction with the air-water & carbon-water interfaces 2) Fluid shearing forces during wicking"
-Bob Glaeser
The AWI is a warranted scapegoat
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