Ever wonder if nature already 'invented' RNA-guided transcription factors like CRISPRi/a? Then look no further... we found many examples of domesticated, nuclease-dead TnpBs that use guide RNAs to repress genes! In bacteria AND phage! A wonderful team effort led by Tanner Wiegand
New pre-print from the Sternberg Lab! Transposon-encoded nucleases (TnpB/IscB) gave rise to the CRISPR-associated proteins (Cas9 and Cas12), but were TnpB-like proteins domesticated for other functions? 𝙔𝙀𝙎!!
Nobels are also bittersweet, because SOOO many more folks deserve the award than can receive it. Michael ‘Michi’ Hauer was the first to purify Cas9 in Jennifer’s lab, whole working with Martin Jinek. He died last year, but would have been ecstatic to hear the news today.
A lot of emotions this week. This award is thanks to an AMAZING group of students/postdocs/technicians in the lab, who make coming into lab every day a real treat. Can't wait for all the discoveries we'll continue to make together :)
Zoom celebration of Jennifer's Nobel, with large D-Lab contingent joining in. As always, Jennifer crediting the many people that were so critical to the work in her lab.
My lab's first paper came online today, the result of a thrilling project with my first three PhD students, led by the brilliant
@SanneKlompe
. See her *first* Twitter thread below to learn more... and follow her! (And also follow
@sternberglab
:)
Hey Twitter! I'm super stoked to plug the first paper from the Sternberg Lab! Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration (). Some takeaways from our paper: 1/8
Thrilled to see our latest work published this week, on the essential roles of IscB/TnpB -- ancestral homologs of Cas9/Cas12 -- in transposon maintenance & spread. A wonderful team effort led by the talented Chance Meers! Thread on bioRxiv version below...
Great news - our lab's latest manuscript is out on bioRxiv!
Led by postdoc Chance Meers, we discovered that RNA-guided DNA cleavage by transposon-encoded nucleases arose to facilitate the pervasive spread and inheritance of transposons. 🧵: (1/6)
Jennifer Doudna: amazing mentor, scientist, writer, etc. Also always down for a good party. Here we dragged her and
@jhdcate
to check out the
@ForeverlandBand
at Bimbo's 365 Club in SF. She's got some wicked dance moves!
Our newest manuscript is live on bioRxiv! Beautiful work led by Leo
@Vopinator
in the lab, for high-efficiency, multiplexed DNA insertions in bacteria using CRISPR RNA-guided integrases. A great collaboration w/
@RondaCarlotta
and
@harriswangnyc
. 1/n
I'm really excited for this work to finally be published! Fantastic team effort from my colleagues
@CaribouBio
(especially Peter Cameron),
@StanBrouns
, and others. It's been fun seeing Cascade and Type I CRISPR systems get some time in the spotlight this year :)
I'm excited to share our recent work exploring the role of IscB/TnpB nucleases in transposition... which helps explain the mysterious evolutionary origins of RNA-guided DNA cleavage by Cas9 & Cas12!
A great team effort led by Chance Meers. Read more in Sanjana's thread below!
Great news - our lab's latest manuscript is out on bioRxiv!
Led by postdoc Chance Meers, we discovered that RNA-guided DNA cleavage by transposon-encoded nucleases arose to facilitate the pervasive spread and inheritance of transposons. 🧵: (1/6)
BREAKING NEWS:
The 2020
#NobelPrize
in Chemistry has been awarded to Emmanuelle Charpentier and Jennifer A. Doudna “for the development of a method for genome editing.”
We were lucky to have Dr. Jennifer Doudna join our Precision Medicine course
@Columbia
yesterday as a special guest! The timing was fortuitous, as our topic was the potential of CRISPR technology to cure disease, alongside critical ethical and societal considerations.
@igisci
I'm thrilled to share our new study out today in
@Nature
on the role of TnsC in enhancing the fidelity of RNA-guided transposition. A wonderful collaboration with
@IsraelF96135088
. For more info, check out lead author Florian's (
@fthoffmann
) thread below!
Excited that our paper is now online
@Nature
! Selective TnsC recruitment enhances the fidelity of RNA-guided transposition - the result of a fantastic collaboration of the
@shsternberg
and
@IsraelF96135088
labs. () A thread:
1/10
Exciting new work from the lab, on the marriage of transposons, CRISPR-like nucleases, guide RNAs, and self-splicing ribozymes! Check out the thread below from (Twitter-less) lead author, Rimante. A wonderful team effort
We’re beyond excited to share the newest pre-print from the Sternberg Lab! You thought all bacterial transposons (aka IS elements) were simple? Think again…🤓1/6
Massively proud of Leo's elegant & thorough study out in NBT, developing CRISPR-transposons for high-efficiency & high-fidelity DNA integration in diverse bacteria. Lots of exciting ideas on advancing this even further, together w/ collaborators
@harriswangnyc
and
@RondaCarlotta
My first author paper is out today
@NatureBiotech
! We describe efficient and multiplexed engineering of bacteria using our CRISPR-transposon system INTEGRATE. Huge thanks to
@shsternberg
for his guidance, and to our amazing collaborators
@RondaCarlotta
and
@harriswangnyc
!
Today we report the characterization of 18 new Type I-F RNA-guided transposases in
@MolecularCell
, with many showing high-efficiency & high-fidelity DNA integration. PDF link below, and great 🧵 from lead author
@SanneKlompe
So happy to share that we’re now online
@MolecularCell
! Evolutionary and mechanistic diversity of Type I-F CRISPR-associated transposons (CASTs). Here are some takeaways from our paper (). 1/8
We're hiring! Join the Biochemistry and Molecular Biophysics department here at Columbia, in wonderful NYC, and pursue your best scientific ideas amidst fantastic colleagues and a growing community.
Happy to answer any questions about the department or application process.
Who would not want to start the independent career working with this amazing group of junior faculty? Having peers that get you, share your problems, and can have a drink with you at the end of the week is key for success! BMB is hiring- please apply:
Really proud to share George & Rebeca's work applying CAST systems for targeted DNA integration in human cells, out today in NBT! I'm thankful for contributions made by all co-authors, and excited for more work that is still to come! Check out the🧵below
George & Rebeca here for the Sternberg Lab's inaugural tweet! We are excited to describe the reconstitution of CRISPR-associated transposases (CASTs) in human cells for programmable DSB-free insertion of large DNA cargo at genomic loci
@NatureBiotech
🧬 1/8
So proud of this heroic effort from Tyler in the lab, working together with the brilliant Israel Fernandez
@IsraelF96135088
, in which they solved structures of TniQ-Cascade. Our first glimpses into the molecular basis for RNA-guided DNA integration by CRISPR-transposons. Kudos!!
Thrilled to post this preprint, the result of a really fun collaboration with
@IsraelF96135088
led by the very talented Tyler
@HalpinHealy
! Our first glimpses into the machinery that directs RNA-guided DNA insertion, and how CRISPR and transposition proteins work together!
Lots of great vibes at
@CSHL
CRISPR meeting this week. What a thrill to see
@SanneKlompe
give a fantastic talk to kick off the meeting, followed by George & Rebeca (Twitterless) presenting their poster to a non-stop crowd for 3 hours. Volleyball match w/ friends capped the week
Finally! Our plasmids for leveraging programmable integrases for high-specificity RNA-guided DNA integration in bacteria are now available at Addgene. Enjoy :)
Thrilled to see
@SanneKlompe
recognized with this award from
@RNASociety
— very well deserved, for her discovery and exploration of CRISPR RNA-guided transposases!
Big update: we're hiring a new lab manager!!
Come join a fantastic group of scientists in the
@SternbergLab
at Columbia University, in the heart of New York City, and contribute to cutting-edge CRISPR and genome engineering research. Please re-post and DM me with your interest
The Sternberg Lab is recruiting postdocs! Our new paper is out, and we have more ideas and ongoing projects than we can possibly do ourselves. Come join us!! Biochem/biophys/genetics/structure/gene editing/...
Please retweet!
What a day! We had such a blast sharing our science with middle-schoolers in Long Island, at the inaugural Cutting-Edge Science Camp! Big shout-out to all the volunteers from
@Columbia
, and to
@SawickiScience
@jameshmccabe
@dharls1
@WenWanso
and all the teachers from East Meadow!
This breaking news story sure is an absolute bombshell for the
#GeneEditSummit
in Hong Kong this week. No doubt countless speakers are scrambling to update slides as we speak. All of a sudden the message is shifted from "should we" to "oh shit someone did it, now what?!"
Yesterday was my first day
@Columbia
! I'm incredibly stoked to be in such an inspiring environment and have the opportunity to work with amazing scientists here. Day 1 highlights: Landweber group meeting, orientation with my fantastic dept staff
*stock photo (not from my office)
Exciting new work on the molecular basis of "off-target" (➡️ untargeted) DNA integration events with type V-K CASTs, led by the talented
@jerrintgeorge
. Punchline: these transposases are more prone to CRISPR-independent transposition. See the 🧵 below...
We are super excited to share our work unraveling the mechanistic intricacies of target site selection by type V-K CRISPR-associated transposases now available as a preprint on bioRxiv!🧬
1/16
Incredible line-up of talks to celebrate Joachim Frank’s 80+ birthday today
@ColumbiaPS
. Peter Moore just gave a captivating survey of ribosome work over the decades, starting with 1950s images of rough ER, to early crystal structures, to CryoEM. Crazy how far the field has come
Many humbling firsts for me in the new job. Yesterday's faculty meeting, Richard Axel presenting, was great. (
@joachimfrank
missed you there). And then just now,
@rubenlgonzalez
, my undergrad advisor, sitting in MY office 12 years after he gave me my first research opp
Last time at UC Berkeley seeing Jennifer
@doudna_lab
and
@jhdcate
, before my move to Columbia. Bittersweet goodbye for sure, excited for the next step but will miss this place!
A question for the community:
Six months ago,
@IsraelF96135088
posted our new cryoEM manuscript on
@biorxivpreprint
bioRxiv, which was a follow-up to the CRISPR-transposon discovery we published the month before. The cryoEM paper just came out in Nature last month. 1/n
We had a blast geeking out on all things Tn7 / transposon / CRISPR with
@JoePetersLab
at Columbia over the last few days. Thanks for a fantastic talk and visit Joe, looking forward to many more discussions to come... :)
Check out this thread from
@mattwalkerhi
on exciting new work from the lab, dissecting transposon end requirements of CASTs using pooled libraries and HTS. Very proud of the collaborative effort from Matt, Dr.
@SanneKlompe
, and Columbia undergrad
@DennisJZhang1
!
@ColumbiaBiochem
Thrilled to release our manuscript on biorxiv!
@SanneKlompe
and I investigated a CRISPR-associated transposon (CAST), uncovering a novel cellular factor and molecular requirements that will be critical for genome engineering. (1/7)
Hey CRISPR peeps: what's your favorite algorithm/software for identifying potential protospacer matches from a list of spacers (or a CRISPR array)? I've used CRISPRTarget () in the past but am wondering if there's anything newer/better. Thanks for the help!
Super cool! Watch Cas9 pop off DNA. I think the audible gasp at CRISPR 2017 meeting when Nureki played this video was one of largest reactions I've heard to new data being presented.
Thrilled to see this paper from Zucai Suo's lab. It is often ignored/forgotten that Cas9 does NOT generate blunt DSBs, but can resect non-target strand extensively. Has importance for DNA repair outcomes in gene editing experiments
Just got off phone with a colleague of mine,
@EricFormanMD
, who’s lab director of Columbia University Fertility Center
@ColumbiaWomens
. Learned quite a bit about standard practices (in the US at least) for the application of IVF with HIV discordant couples. Some take-homes... 1/n
Excited to see this paper published! Beautiful work from Mike, Popo, and
@JoePetersLab
on target site selection by CRISPR-transposons using cryptic, privatized guide RNAs. Congrats!
There's been recent reports of the crystal structure of
#COVID19
. But now the crystal structure of the antibody, derived from a patient who recovered, w/ implications for vaccine devp't So proud of my colleagues
@scrippsresearch
h/t
@hholdenthorp
Been checking out Jiankui He's website. His academic training is in single-cell sequencing (no publications related to CRISPR & assisted reproduction), and his embryologist collaborator, Jinzhou Qin, received his PhD in 2016 --> just 2 years ago! Insane
What an amazing visit! I am honored that you and your students welcomed me and my lab into your classroom this year, and I had a blast learning about your CRISPR experiments today. Let’s do it again next year!!
Can't wait to read this paper. Was wondering when we'd see a paper from David Liu's lab applying PACE to Cas9 directed evolution. Interested to see what we can learn about how PAM recognition is tied to DNA interrogation & specificity. Many times was asked about a "PAM-less Cas9"
Stunning. The scientist purportedly responsible for the birth of world's first gene-edited babies describes the work. "I understand my work will be controversial, but I believe families need this technology and I'm willing to take the criticism for them."
Super cool! Somewhere between 260 million to 7 billion viruses per square meter are deposited *every day*, after being aerosolized and traveling through the free atmosphere. Wowza.
Huh? The dCas9 mutation in Qi et al. (2013) was actually H841A, not H840A? But S. pyogenes Cas9 has isoleucine at position 841. I'm confused...
@stanleyqilab
h/t
@joeBondyDenomy
Excited to see this out -- congrats!
(Now I have a link to share, as I keep telling colleagues to think (more) carefully about reaction buffer conditions! :)
I'm excited to share our findings on a metal-dependent specificity switch for
#CRISPR
-Cas12a! We profiled the specificity of Cas12a at four Mg2+ concentrations and observed striking differences in mismatch tolerance at lower, physiological conditions 1/n
Exciting stuff - congrats everyone! It was one of my favorite talks at the conference (and reminded me of Martin and Krzysztof’s tag team talk in 2012). Bonus was hearing
@irma_querques
present it again to our lab on Friday in person.
What I don't understand: message of article is again to prevent genetic disease, and core principle
#2
is "Only for serious disease." But there are other ways to prevent vertical transmission of HIV, so their clinical use doesn't even seem to follow their own guidelines!
New in
@CRISPRjournal
:
He Jiankui’s group proposes a set of 5 core values to frame, guide, and restrict clinical applications of gene editing technologies.
#GeneEditSummit
After a fantastic symposium this morning on coronavirus/COVID-19 research happening at
@ColumbiaMed
, and a chat just now with some students leading a huge effort to review new literature coming out, I am feeling inspired and honored to be part of this community.
@Columbia_CRAC
Beautiful work, Joe et al., wow! We had a great lab journal club digging deep into this work yesterday and really enjoyed the manuscript - congrats! CRISPR-transposons continue to amaze...
Guide RNA categorization enables target site choice in Tn7-
#CRISPR
-Cas transposons Allows access to new plasmids and phage for horizontal transfer while keeping long-term memory of safe sites in bacterial chromosomes
@IsraelF96135088
@biorxivpreprint
On the other hand, I'm questioning the value and benefit of making our work available as a preprint in advance of publication, when multiple groups essentially copied our study and tried to beat us to press.
Thoughts? What lesson do we take away from this, for next time? 3/3
A new article about CRISPR and gene editing from
@WalterIsaacson
gives an exciting preview of what I'm sure will be a fantastic (future) book on the topic. Exciting to see our recent work mentioned on CRISPR-containing transposons, or 'jumping genes.'
Been feeling a bit down/anxious with all the depressing news lately... this is helping. (Thanks to NPR for the album review earlier)
Mixing Colours by the Eno brothers
Check out Diego's 🧵and excellent protocol on how to best harness CRISPR-associated transposases (CASTs) for bacterial genome engineering. We hope it will be a great resource for the community!
Never too late to share
@SternbergLab
's first Nature Protocols! Interested in editing your favorite bug? 🦠 Check out our protocol describing a novel and versatile CRISPR-associated transposase (CAST) system for targeted insertion of large DNA payloads into bacterial genomes.
Amidst this crazy CRISPR news cycle, what a welcome break to participate in
#SkypeAScientist
and video-conference with a high school classroom from Burns Flat, OK. Great questions, enthusiasm, interest in the research, the technology, the ethics, and how to become a scientist!
Help: Is there any way in the new Pubmed to have the results automatically sorted by "Most recent," instead of (annoyingly) having to select this from the Display Options dropdown every time??
Some exciting synergy with another preprint just out from
@doudna_lab
and
@BanfieldLab
... congrats to all the authors involved in that story! It's clear that RNA-guided integrases are going to be a powerful new addition to the genome engineering toolkit
An elegant and creative study to convert Type V-K CAST systems from copy-and-paste into cut-and-paste transposases - congrats!
(I'm still very curious what biological factors drove different transposition behaviors... why replicative sometimes, non-replicative others?)
Today in
@biorxivpreprint
, we describe the development of HELIX, an advance that markedly improves properties of type V-K CRISPR-associated transposases (CASTs) for programmable, cut-and-paste, multi-kilobase DNA integration. 1/14 🧵👇
Congrats on this excellent story, Josh et al.! Who would've thought that Type II CRISPR-Cas systems encoded a natural single-guide RNA all along! Another cool example of Cas effectors being repurposed for non-canonical (non-nuclease) fxn, in this case transcriptional repression
Excited to announce the maiden voyage of the Modell lab, led by the outstanding
@reworkman0
and
@tejapammi
. We found S. pyogenes Cas9 uses a natural single guide RNA, a conformation of the 171nt tracrRNA, to transcriptionally repress its own promoter.
Prediction: 2018 will be remembered as the landmark year in which humans first began rationally modifying the genetic material of their offspring, and in doing so, taking direct control over evolution
Holy crap. Had no idea a Hollywood movie was coming out featuring CRISPR. And starring The Rock no less. His tweet might top Ashton Kutcher's for funniest/coolest CRISPR celebrity shout-out
Great RAMPAGE review from my fellow Science majors. We wanted to utilize real CRISPR technology as our scientific backdrop. Of course I still screw up what this acronym means. 🤷🏾♂️
Excited to be co-hosting an RNA Salon at Columbia University, together with colleague Laura Landweber. Monthly seminars featuring research across Columbia's campuses focused on RNA!
@RNASociety
@Columbia
Thanks for the wonderful News and Views, Fyodor! I had no idea you were writing this, and I couldn't be happier. I may just cite this more often than our own paper... ;)
Our future of "Editing as medicine" has a new actor (only an understudy for now): a CRISPR "borrowed" from bacteria by its parasite. Mother Nature truly rocks in how creative she is - as shown in beautiful, and real-world-resonant, work by
@shsternberg
.
Interesting that most of this video focuses on using gene surgery to avoid children suffering from genetic disease. But the edit made to Lulu and Nana's genome was (apparently) an elective mutation of CCR5 to achieve HIV resistance, not a change to prevent an unavoidable disease
"If the Model T was prone to overheating, Crispr Classic is prone to overeating." 🙄
Is anyone else slightly irked that journalists are now often writing "Crispr" instead of "CRISPR"? I know NYT has a silly policy on acronyms, but Wired too? And WSJ?
I had a blast Chris! East Meadow has some really bright 7th graders and incredible teachers. I’m excited to keep our partnership going and hear about their CRISPR experimental results in June!
Speaking of RNA,
@hauke_hillen
gave a fantastic seminar here yesterday on his studies of mitochondrial transcription. What a pleasure to host him and spend a few days catching up and talking science. We were
@doudna_lab
buddies back in 2012!
In our new pre-print, we demonstrate that 3D genome organization around nuclear speckles controls the efficiency of mRNA splicing.
Check out my thesis work
@Caltech
in this thread by
@mitchguttman
!
@4DNucleome
#Genomics
Just now remembering that the book I wrote with
@jadoudna
on CRISPR gene editing is presently being translated into Chinese for 2019 publication, and the publisher is expecting us to author a new forward. Today's development adds an interesting new element to that....