@HMSgenetics professor studying RNA dynamics across the cell, including transcription, mRNA processing, and mitochondrial gene expression. @Stanford physics PhD
Cambridge, MA
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I'm thrilled to see the cover of @NatureSMB this month! My sibling Leidy Churchman made this special painting to illustrate our latest work on the packaging of mitochondrial DNA. Both works are nicely described in the "Musings on art and science" editorial
nature.com/articles/s41594-0…
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It’s official, the best lab website is the Heiman lab website! It’s a must see, but make sure you have some time to kill. heimanlab.com/cgi-bin/heiman
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How does RNA flow through the cell? From their synthesis, chromatin release, nuclear export, ribosome engagement, and eventual degradation, we quantified the lives of human transcripts genome-wide. (1/7)
See @BrendanSmalec and @robertietswaart ‘s preprint
biorxiv.org/content/10.1101/…
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Splicing of human introns could occur in any order across an RNA, which combinatorially adds up to thousands of possible splicing orders for a typical transcript. Are all orders used? Read our latest preprint by @Karine_Choquet to find out! (1/6) biorxiv.org/content/10.1101/…
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Ever had a list of gene hits and not known what to do? Maybe GO enrichment left you wondering what your favorite gene is doing in your experiment? Check out GeneWalk, our #ML method that determines the relevant functions for each gene @robertietswaart (1/4)biorxiv.org/content/10.1101/…
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GeneWalk is now published! Ever had a list of gene hits and not known what to do? Maybe GO enrichment left you wondering what your favorite gene is doing in your experiment? GeneWalk determines the relevant functions for every gene hit! @robertietswaart
GeneWalk, from @robertietswaart, @fiddle and co, is a method for prioritizing genes from a gene list. Given a list of genes, eg from RNA-seq experiment, it constructs a regulatory network and uses GO annotations to identify the most relevant genes. genomebiology.biomedcentral.…
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How are the hundreds of copies of mitochondrial DNA packaged in our cells? It’s a mystery because histones and chromatin factors are not in mitochondria and the high copy number presents challenges! Read what Stefan @rsisaac found in our preprint. (1/7)
biorxiv.org/content/10.1101/…
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Our protocol for direct sequencing of nascent RNA is now published! Nanopore analysis of CO-transcriptional Processing (nano-COP) took us four years to get right. In this protocol, we describe the final approach *and* how we got there. (1/3) rdcu.be/cergf
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Human genes have so many introns! When and how are they all spliced out? Does splicing follow the order of transcription? Are neighboring introns spliced cooperatively? These fundamental questions are crucial to our understanding of splicing regulation. (1/4)
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Human respiratory complexes are encoded on both nuclear and mitochondrial DNA. Is gene expression coordinated across these genomes that are expressed in separate compartments and by different factors? Read our latest preprint to find out! (1/7)
biorxiv.org/content/10.1101/…
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How does Pol II navigate the crowded, complex chromatin environment, surrounded by nucleosomes and other transcriptional activity? We are excited to share our preprint, a fantastic collaboration with @stergachislab, led by Tommy Tullius @mtcicero26
biorxiv.org/content/10.1101/… (1/5)
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How are nuclear and mitochondrial DNA co-regulated to achieve balanced oxidative phosphorylation (OXPHOS) subunits? We performed a CRISPR screen to identify human genes that maintain mitonuclear balance. See our preprint by Nick Kramer and @GyPrak (1/4) biorxiv.org/content/10.1101/…
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🎉Our paper quantifying how RNA flows across subcellular compartments is published! 🎉
Read more in the preprint thread ⬇️ The paper contains an improved analysis of RNA flow rates and new collaborative work on DDX3X with @stephenfloor
authors.elsevier.com/a/1jMoV…
@MolecularCell
How does RNA flow through the cell? From their synthesis, chromatin release, nuclear export, ribosome engagement, and eventual degradation, we quantified the lives of human transcripts genome-wide. (1/7)
See @BrendanSmalec and @robertietswaart ‘s preprint
biorxiv.org/content/10.1101/…
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Another new preprint! “Regulatory principles of human mitochondrial gene expression revealed by kinetic analysis of the RNA life cycle.” Let us walk through a day in the life of a mitochondrial RNA. @ErikMcshane led this beautiful study. (1/n)biorxiv.org/content/10.1101/…
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🎉Our paper "Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression" is now online! 🎉
nature.com/articles/s41556-0…
Summary ⬇️but the published manuscript is greatly expanded! Congratulations to Nick Kramer, @GyPrak thanks to @KanarekNaama for collab.
How are nuclear and mitochondrial DNA co-regulated to achieve balanced oxidative phosphorylation (OXPHOS) subunits? We performed a CRISPR screen to identify human genes that maintain mitonuclear balance. See our preprint by Nick Kramer and @GyPrak (1/4) biorxiv.org/content/10.1101/…
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Some of the highest expressed genes in our genomes are encoded by mitochondrial DNA. To understand how and why, we developed new methods that uncover the many quirks of mtDNA expression. Find out what we learned in our recent review by @ErikMcshane and me. academic.oup.com/hmg/article…
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🎉 🎉Our paper, "Single-nucleoid architecture reveals heterogeneous packaging of mitochondrial DNA," is now published! rdcu.be/dyqzP @NatureSMB
See the tweets below ⬇️ for a summary. Congratulations to the whole team! @rsisaac @mtcicero26 @stergachislab 🎉🎉
How are the hundreds of copies of mitochondrial DNA packaged in our cells? It’s a mystery because histones and chromatin factors are not in mitochondria and the high copy number presents challenges! Read what Stefan @rsisaac found in our preprint. (1/7)
biorxiv.org/content/10.1101/…
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This is an original oil painting by my sibling, Leidy Churchman. I still can't believe @Nature passed on it. I love this painting so much. In the end, Leidy sold it to a collector at @ArtBasel. @MurrayGuyInc @MatthewMarks
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Ever wonder how mitochondrial and nuclear genes are coregulted to produce functional mitochondria? Here’s our review discussing what is known and all the work that needs to be done on: The Multiple Levels of Mitonuclear Coregulation annualreviews.org/doi/abs/10…
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My host spent a good hour telling me how eating meat is terrible for global warming, which I agree with but... I like bacon too much, I told him. At the dinner, everyone ordered vegan entrees clearly in deference to the host. I got the lamb chops, but not the job!
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Our latest preprint describes the high-resolution role of 41 factors in yeast transcription elongation using NET-seq. The 9-year multi-generation effort was lead by three first authors. Congratulations to @lachance_kate, @KharMT, and Mary Couvillion! biorxiv.org/content/10.1101/…
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I joined twitter ten years ago today and here's my first tweet. It was the day I first dreamt up ideas for what would become NET-seq!
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Strong cell growth requires fast ribosome assembly, so proliferating cells dedicate nearly half their protein/RNA biomass production to new ribosomes. But at what cost? Our latest paper on bioRxiv addresses this question. 1/4 biorxiv.org/content/early/20…
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🎉Our paper "RNA polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation" is now published in @Dev_Cell, a fantastic collaboration with @bloodgenes led by @Danyajane. See tweets ⬇️ for more! 🔴🔴🔴🔴🔴
authors.elsevier.com/a/1hbDZ…
Does Pol II pausing control cell differentiation? @Danyajane, in collaboration with @bloodgenes, studied Pol II pausing and SPT5 in human erythropoiesis and found Pol II pausing temporally coordinates cell cycle progression and erythroid differentiation. medrxiv.org/content/10.1101/…
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We're looking for a PhD-level research scientist! Come help us elucidate how gene expression processes are coordinated, from the nucleus to the mitochondria. If you are considering a non-PI career path, but want to stay in academic research, please apply! sjobs.brassring.com/TGnewUI/…
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🎉Our paper on the challenges and resolution of balancing nuclear and mitochondrial gene expression is out! @ErikMcshane's deep dive into every step of mitochondrial gene expression is wild! 🎉
See tweets ⬇️ and the @MolecularCell article for much more. sciencedirect.com/science/ar…
Another new preprint! “Regulatory principles of human mitochondrial gene expression revealed by kinetic analysis of the RNA life cycle.” Let us walk through a day in the life of a mitochondrial RNA. @ErikMcshane led this beautiful study. (1/n)biorxiv.org/content/10.1101/…
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Wonderful to see our work on human mito-nuclear balance published! We found that the synthesis of mitochondrial- and nuclear-encoded OXPHOS subunits are remarkably balanced in the 5 cell types we studied. Thanks @Antonio41949078 Barrientos lab for the collaboration.
Soto, Couvillion, @fiddle & co study ribosome profiling data and uncover translational control to help equalize expression of mitochondrial and nuclear-encoded OXPHOS subunits. Imbalanced translatomes activate stress response. genomebiology.biomedcentral.…
ALT Schematic of information flow between mitochondrion and nucleus, and a graph of the relative expression levels of different OXPHOS complex subunits
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It's finally out! Lots of new data since the pre-print we posted last May.👮
Splicing Kinetics and Coordination Revealed by Direct Nascent RNA Sequencing through Nanopores dlvr.it/RRJdV3
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I’m thrilled to share our latest paper analyzing RNA polymerase globally at single-molecule resolution that provides a glimpse into the vast potential of single-molecule genomics. See tweets below for the overview, and read the paper for the full story! sciencedirect.com/science/ar…
How does Pol II navigate the crowded, complex chromatin environment, surrounded by nucleosomes and other transcriptional activity? We are excited to share our preprint, a fantastic collaboration with @stergachislab, led by Tommy Tullius @mtcicero26
biorxiv.org/content/10.1101/… (1/5)
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Congrats to @Umut1Eser on our paper describing the ground state and evolution of promoter directionality! cell.com/cell/fulltext/S0092…
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In this preprint we describe @nanopore analysis of CO-transcriptional Processing (nano-COP) that directly sequences nascent RNA. With human and Drosophila data, we answer the above questions and shed light on how splicing patterns are achieved (2/4)
biorxiv.org/content/10.1101/…
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Our preprint on splicing dynamics in human cells is now published with 5x more data! Congratulations to Heather and Karine! cell.com/molecular-cell/full…
All @nanopore data are here: ncbi.nlm.nih.gov/geo/query/a… and all analysis scripts are deposited: github.com/churchmanlab/nano…
In this preprint we describe @nanopore analysis of CO-transcriptional Processing (nano-COP) that directly sequences nascent RNA. With human and Drosophila data, we answer the above questions and shed light on how splicing patterns are achieved (2/4)
biorxiv.org/content/10.1101/…
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Congratulations to Andrew Stergachis and John Stam for developing such a powerful and straightforward approach to analyze chromatin fibers at the single molecule level! It was a blast to work with them on this.
Single-molecule regulatory architectures captured by chromatin fiber sequencing science.sciencemag.org/conte…
Fiber-seq: Single-molecule long-read sequencing of chromatin stencils enabled nucleotide-resolution readout of the primary architecture of multikilobase chromatin fibers
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In my graduate lab we had a “live” webcam video on our homepage. But it was actually a video loop of my bay mate pipetting sped up 1.5x. People would be like, I went to your website last night and saw David pipetting furiously at 10 PM!
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2021 Churchman lab retreat! It was a local one this year with chalk talks in the garden. @HopeMerens got us started!
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Watt Webb was my undergraduate mentor. And remains my role model.
I walked into his office sophomore year and asked for a job, any job. I was a physics major with little to no understanding of biology. But I was curious. I started by sweeping the floors, literally (1/n)
Biophysical Journal Call for Papers
Special issue dedicated to Watt W. Webb: Point spread functions—from fluorescence correlation spectroscopy to multiphoton microscopy
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Our paper, "Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness" is now online! Read the summary below, but the full paper has new MS data from @MartinWuhr! Thanks also to Mike Springer, David Pincus and @NikkiCommins for the collab! elifesciences.org/articles/4…
Strong cell growth requires fast ribosome assembly, so proliferating cells dedicate nearly half their protein/RNA biomass production to new ribosomes. But at what cost? Our latest paper on bioRxiv addresses this question. 1/4 biorxiv.org/content/early/20…
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Join Mike Levine and me for a hybrid Keystone meeting on Gene Regulation! We have incredible speakers and will select many more from abstracts
@mooreorless62 @IbrahimCisse_ @CramerLab @mayer_lab @AsifaAkhtar1 @DePaceLab @EKFarley @sandberglab @drosoigmm @tinekelenstra @youngricka
Discover the latest in #GeneRegulation #transcription factors, #RNA & more with @fiddle @ChurchmanLab at the January @KeystoneSymp in Santa Fe.
Scholarships applications are open to students, post docs & LMIC scientists, due Oct. 7.
keystonesymposia.org/KS/Onli…
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I'm excited to read this one as I've always wondered about the impact of GFP tags: Systematic assessment of GFP tag position on protein localization and growth fitness in yeast. biorxiv.org/content/early/20…
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A silver lining to @harvard classes being online is that I get to learn about black holes just hanging out in the living room. @andystrominger is in our kitchen teaching his ever popular "black holes and cookies" freshman seminar over zoom. Sadly this year, no cookies.
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If you’re interested in what the last few years have taught us about the process of splicing, check out our latest review!Congratulations to my co-authors @HopeMerens @karine_choquet @Autum_BaxterKoe
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Wow, we’re on a role! Two covers in two months! For two fascinating stories on the fundamentals of mitochondrial gene expression!
Very excited to see our work featured on the cover of the latest edition of Molecular Cell. Check out our manuscript to learn more about how the nuclear genome works together with the highly polyploid mitochondrial genome across the cell.
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Dark and uplifting at the same time. Beautiful quote.
"The effort to understand the universe is one of the very few things which lifts human life a little above the level of farce and gives it some of the grace of tragedy."
- Steve Weinberg, The First Three Minutes
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We've started daily "standup meetings" on zoom. They get teams together quickly and frequently for <15 minutes. Everyone answers the following: 1) What did you accomplish yesterday? 2) What are your goals today? 3) Are there any barriers to your progress? highfive.com/blog/5-steps-ru…
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Happy to see @karine_choquet's paper published!
"Pre-mRNA splicing order is predetermined and maintains splicing fidelity across multi-intronic transcripts."
See the preprint tweetorial or full results with expanded analysis: nature.com/articles/s41594-0… @NatureSMB @RouskinLab
Splicing of human introns could occur in any order across an RNA, which combinatorially adds up to thousands of possible splicing orders for a typical transcript. Are all orders used? Read our latest preprint by @Karine_Choquet to find out! (1/6) biorxiv.org/content/10.1101/…
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I love this video describing our work led by @ErikMcshane! Thanks to everyone who helped put it together. cell.com/molecular-cell/full…
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My first tweet from 2007 says "Thinking about RNA polymerase". 7 years later, and it's all I think about.
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I pulled up my thesis defense talk from ten years ago and realized I put shadows under my slide titles. <shudder> I've come a long way!
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If you’ve ever seen me give a talk, you’ve probably seen one of my brother’s paintings. If you’re in New York between now and April 18, I highly recommend his show at @MatthewMarks Gallery. I loved the layers of beauty, emotion and meaning in each piece!
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20 years ago, it was daunting to be a physics PhD student as only 10% were women. Remarkably, the statistic has not changed since. So proud of my husband @andystrominger whose high energy theory group is half women. Read about his mentoring style @GenHET_ drive.google.com/file/d/1x-D…
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You can stop your search because there is no better lab webpage than @maxwellheiman's page: heimanlab.com/cgi-bin/heiman
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Does Pol II pausing control cell differentiation? @Danyajane, in collaboration with @bloodgenes, studied Pol II pausing and SPT5 in human erythropoiesis and found Pol II pausing temporally coordinates cell cycle progression and erythroid differentiation. medrxiv.org/content/10.1101/…
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We show that splicing completes after many kilobases are transcribed, but sooner in flies than humans. We find that splicing does not always follow the order of transcription and that human splicing is coordinated across proximal introns. Much more in the pre-print! (4/4)
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My graduate advisor told us that luck is the ability to recognize opportunity when it arrives. I like thinking of it that way. nitter.app/ellabellableu/status/8…
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Looking forward to celebrating Stephen Hawking’s life and science today at Westminster Abbey. He’ll have great company between Newton and Darwin.
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Curious about black holes? Check out: Black Holes: The Edge of All We Know on @netflix featuring my husband @andystrominger who explains why he thinks about them 24 hours a day, seven days a week, even when he’s brushing his teeth and when he’s dreaming. theguardian.com/film/2021/ma…
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Our first biorxiv paper: FIDDLE accurately predicts datasets, like TSS annotation, from data you already have. @Umut1Eser
FIDDLE: An integrative deep learning framework for functional genomic data inference biorxiv.org/cgi/content/shor… #bioRxiv
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I strongly approve and support the @harvardmed diversity statement released today. It reflects the HMS I know and the leadership of Dean @G_Q_Daley. Thanks to all at HMS who helped put it together and I look forward to helping fulfill its promise! hms.harvard.edu/about-hms/ca…
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Bird watching out my office window! A red-tailed hawk couple is raising eyas in the nest in the bell tower of the @BostLatinSchool. @HMSGenetics @harvardmed
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Feeling stupid is so important! Highly recommended. nitter.app/debellerochelab/status…
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Exited for @HMSGenetics holiday party where we’re testing how elevated our palates are! Aliquots of liquids, from wine to whiskey, have been distributed and now we guess what they are and which are expensive! Thanks to @_emmarosewest, @vonshannon and @BrendanSmalec for organizing
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I had a great time presenting to all the Damon Runyon fellows. I have such fond memories of the retreats. And I got the most questions I’ve had in a while! Thanks for all the stimulating conversations!
We’re honored to have L. Stirling Churchman, PhD, of @HarvardMed as today’s alumna speaker. She is speaking on the “Dynamics of gene expression and academic careers” @ChurchmanLab #DamonRunyonRetreat
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Celebrating Jack Strominger’s 99th New Year’s Eve! Happy New Year to everyone! May we all enjoy so many.
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One week left to submit your abstract to the EMBO workshop on Chromatin and Epigenetics! Check out the speakers! We worked hard to include new and exciting directions in chromatin biology. Hope to see you there!
Submit your abstract by 13 Feb for the EMBO Workshop: Chromatin and Epigenetics, #EMBOchromatin #chromatin @EMBOevents - buff.ly/2G2oe9u
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Join us! We are looking for a Research Assistant to work on various projects on transcription, mRNA splicing, and mtDNA expression/maintenance. Join our fun, supportive and stimulating lab environment! Feel free to contact me with questions/interest. sjobs.brassring.com/TGnewUI/…
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About a month ago, someone here described how a failed experiment was troubleshot by a service that will sequence a whole plasmid for $25. I lost the tweet -- does anyone know of a cheap and fast plasmid sequencing service?
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Chromatin Haiku
If you reveal yourself here
A drink awaits you
@ChromatinHaiku @TriggerLoop #moet2017
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Exceedingly excited that my sibling, Leidy Churchman, was selected to participate in the Whitney Biennial this year. Apr 6 - Sept 5. If you are in New York, please check it out!
The 2022 Whitney Biennial artist list is here.
We're excited to announce the 63 artists that will be featured in Whitney Biennial 2022: Quiet as It's Kept. Co-curators David Breslin and Adrienne Edwards give us a sense of what's to come.
The full list: whitney.org/biennial2022
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Congratulations on your ML approach - great that it makes cryoEM even better and easier! And happy to hear my twitter habit lead to something worthwhile :)
This is many years in the making! I remember tweeting about this 3.5 years ago when @fiddle posed the question - can't we tackle this with machine learning?
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The Churchman lab has a new model organism! Please help us welcome Chlamydomonas reinhardtii!
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Once in your career you might get scooped or screwed but mostly, the science was better and you were happier than if you never shared.
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I'm at a string theory/gravity workshop in western UK where I hoped to hide away and work on manuscripts. Now they have insisted that I give a talk. Advice on explaining gene regulation to theoretical physicists?
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Exciting to be back @CSHL for the #cshlsysbio general expression meeting! Love seeing our data generated by @mtcicero26 and @stergachislab on the poster and abstract book!
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Come join us at @harvardmed! Reach out to me if with any questions especially if you’re wondering whether to apply.
Blavatnik Institute @ HMS has launched a junior faculty search in the Life Sciences - including Genetics - with a specific goal of advancing diversity in scientific research and discovery. Applications invited for up to 4 positions.
academicpositions.harvard.ed…
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Anyone have advice for how to educate family members who trust emails from anti-vaccine groups more than science? Without losing your cool?
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Thanks to #RNA2022 for inviting my student @BrendanSmalec to present his and @robertietswaart work to measure the rates of “RNA flow” across the cell, from chromatin to polysomes!
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Very strange to attend a conference and watch your pre-recorded talk!
First up in our #FlemingShowcase, Dr Stirling Churchman presents her talk on ‘Orchestrating gene regulation across the genome and across the cell’. Read more about Professor Churchman: microb.io/38jcGch @fiddle #WhyMicrobiologistsMatter
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Our review on the RNA Pol II CTD is out. Congrats to @KharMT! The code and beyond: nature.com/nrm/journal/vaop/…
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Many people aren't on Twitter so you don't reach the whole community here anyway. The best way to "self-promote" is to give talks at meetings, publish solid papers, put manuscripts on bioRxiv, be a good citizen in the scientific community, train people well.
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Our new review... Pause & go: from the discovery of RNA polymerase pausing to its functional implications authors.elsevier.com/a/1Untw…
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nano-COP lets you study nascent RNA processing, from transcription-splicing coupling to the order of intron removal across long isoforms. Read more in @hopemerens’s blog post on the protocol. (3/3) protocolsmethods.springernat…
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Disappointing! 1) no ladder, is flight the expected length?, 2) show full blot please! 3) needs a loading control, 4) replicates required.
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Great dinner in Dresden for the ‘Biophysics in the nucleus’ meeting. Great talks today about nucleosome remodeling, phase separation, nuclear stokes fluids @PetersonLab @taekjip @Cisse_lab
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Interested in the sequence determinates of Pol II pausing? Looking for pauses in your NET-seq data? Check out this out 👇
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I had a great visit to @karolinskainst yesterday! Thank you @mitopinionated for hosting me and the fun dinner!
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