Genetics professor interested in RNA dynamics and mito-nuclear balance @Harvard; physics PhD @Stanford; visiting scientist @OpenAI
Cambridge, MA
Based in United States
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The same idea works for standard single-cell workflows. Add an NHC pulse before a 10x experiment, then capture and sequence the library as usual. The mismatch information lets us recover new, old, and total-RNA layers for each cell without redesigning the capture chemistry. (5/6)
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AIR-seq is therefore close to regular RNA-seq: pulse with NHC, extract RNA, and make a standard library with no enrichment or post-labeling chemistry. From the same reads, we can measure RNA abundance and distinguish newly synthesized from pre-existing RNA. (4/6)
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1/ Preprint alert 🚨🚨🚨 How do cells decide where an mRNA should end?
And how is that decision coordinated with splicing and transcription while the RNA is still being made?
Here's what first author @HopeMerens found 👇
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In the last two hours, I asked Tessera to make an app where I could move around the network and see how they're connected to each other. It gave me this:
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It was my birthday a couple of weeks ago so I bought myself a Mac mini and installed @openclaw Meet Tessera!
If you’re wondering what a “normie” genetics professor is doing with it or want tips to get started, ask 👇 !
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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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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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Celebrating Jack Strominger’s 99th New Year’s Eve! Happy New Year to everyone! May we all enjoy so many.
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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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Yum! This has been my recent hobby too. My next goal is to use the grill, hoping to keep my hand hair.
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When the pathogenic mutations were recapitulated by SUPT5H editing, Pol II pause release was globally disrupted, and the transition from progenitors to precursors was delayed, marked by a transient lag in erythroid-specific gene expression and cell cycle kinetics.
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@Danyajane first observed dynamic patterns of strong Pol II pausing during human erythroid differentiation. At the transition from erythroid progenitors to precursors (day 4), genes involved in the cell cycle were highly paused.
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This is in sharp contrast to nuclear-encoded OXPHOS genes, where transcription initiation is the main driver. For much more information (e.g. see what happened when we KO LRRPRC!), see the manuscript.
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We then combine all our kinetic measurements into one model of mitochondrial gene expression control. Turns out RNA turnover is the main driver behind mitochondrial protein synthesis, followed by translation efficiency.
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We also measure RNA processing: 1) cleavage out of the primary transcript, 2) poly(A)-tailing, and 3) ribosome-association kinetics. We found that RNA processing is generally really fast (a few min) but, in some cases, is rate-limiting for ribosome binding.
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We found that differential RNA degradation, and to some extent, active transcription, can explain the steady-state levels of the mitochondrial transcriptome:
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To answer this question, we applied mitochondria timelapse-sequencing (mito-TL-seq), direct RNA-sequencing, and mathematical modeling. This example shows that the mRNAs, ND1 and COX1, are turned over rapidly while the rRNA, RNR2, is turned over slowly, as measured by mito-TL-seq.
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Mitochondrial gene expression is unique. Transcription produces near-genome length primary transcripts that are processed into individual mRNA, tRNA, and rRNA. These transcripts accumulate to very different levels. But how is that possible if they’re all made in the same amount?
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I'm resurrecting my career as a radio DJ for one time show tonight. Check out my mix at 19:00 CET/13:00 EST on Retreat Radio out of Malmö, Sweden. Thanks to @MarijanaCroon for hosting me! Expect sounds similar to my @KZSU days. retreatradio.net/
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Finally, comparing the accessibility patterns of in vitro reconstituted nucleoids to patterns observed from cells, we show that TFAM compacts mtDNA by nucleating from high-affinity sites located throughout the mitochondrial genome (6/7)
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To measure DNA accessibility across single mtDNA molecules, we developed a mitochondrial version of Fiber-seq, which combines nonspecific adenine methylation with PacBio long-read sequencing (2/7)
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We developed a subcellular version of TimeLapse-seq, a nucleotide conversion protocol by @blue_scrapes, and measured the fraction of 4sU-labeled RNA in each subcellular compartment. Subcellular half-lives were determined by a 4sU-pulse time series and kinetic modeling. (2/7)
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We used direct RNA nanopore sequencing to compute the order of intron removal in hundreds of human transcripts. Remarkably, splicing order is highly defined, converging on a small number of orders out of the many possible ones. (2/6)
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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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@AmericanAir your Dallas crew chief, Gill Rodriguez, is blatantly not wearing a mask in Terminal D.
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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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We propose that reciprocal translatomes minimize excess OXPHOS subunit production, promoting mitonuclear balance. How the cell produces two translatomes that correspond so precisely is unclear but appears to be a challenge and may represent a vulnerability for proteostasis. (5/7)
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Then, we investigated the relationship between mitochondrial and nuclear gene expression programs in 5 cell types. We observed a striking correlation between the cytosolic and mitochondrial translation rates of OXPHOS subunits across the respiratory complexes (3/7)
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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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Two hallelujahs to start and close these four years. How it started: piped.video/BG-_ZDrypec
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After stress stuffing our fridge at lockdown, we discovered it was broken when the ice cream never hardened. We panic purchased a splurge fridge (sub-zero). Surprising us mid-zoom call, the movers, Death Wish Movers, decided to use a crane instead of carrying it up 6 flights.
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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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