We hope that this dataset will be useful for those interested in intestinal immunity and circadian biology. Stay tuned for a user-friendly interactive tool from Gabby where you can pick a cell type and follow expression patterns over time.
Examining interactions of plasma cells over time suggests they may receive cues from other cells that are “on the clock”. Makes sense: Perhaps plasma cells deprioritize clock control in favor of mass antibody production (1000s of antibodies/second!) & instead rely on other cells for regulatory cues.
However, terminally differentiated antibody-producing plasma cells have minimal circadian gene expression and few oscillatory genes. Although these cells are “off the clock”, previous work suggests rhythmic production of IgA in the intestine. How?
Some immune cells are particularly “on the clock”: Th17 and innate lymphoid cells have high expression of circadian clock genes. Most immune cells have rhythmic gene expression.
Gene expression patterns suggest that antigen processing in dendritic cells may precede antigen recognition by T cells—temporal coordination of these processes makes sense energetically.
Populations of certain B cell subtypes, including transitional B cells and centrocytes, are extremely dynamic with large shifts over a six hour time frame. TRANSITIONAL B cells indeed.
As expected, there are a ton of naïve B cells (and T cells). The small intestine is a great site for immunological “education”. But what about changes over time?
First, Robert had to call cell types. Intestinal immune cells have quirks compared to other body sites, so he scoured the literature (165 papers over the last 45 yrs). It’s a crime that this work is a single sentence in the paper and one supplemental table.
Here’s what they found using their scRNA-seq data from >815,000 cells:
Then Gabby, a world-class bioinformatician/immunologist/urban farmer/MSTP student in Lora Hooper’s lab, worked her magic. Gabby is so good (& collaborative) that she has been a de facto bioinformatics resource for several labs on campus. Robert also used this opportunity to learn bioinformatics.
So Robert, an immunology aficionado/cat dad/sleep-optional PhD student, used flow cytometry & scRNA-seq to follow mouse intestinal immune cell dynamics at 4 timepoints across the day-night cycle. Chaitanya Dende & Tarun Srinivasan were super helpful with the insane workload and hardcore immunology.
Backstory: We previously found that mice orally infected with coxsackievirus B3 in the morning vs. night had 100-fold different viral titers. Stay tuned for that story—a fun collaboration with John Brooks’ lab at Princeton. But it made us wonder about immune cell dynamics in the intestine.
New preprint/Hooper collab: Ever know a student so passionate about a topic that they dragged you in kicking & screaming but then you were fascinated? Here's how @robertmaples.bsky.social & Gabby Quinn got me to like cellular immunology. (Like, not love. I’m human.) www.biorxiv.org/content/10.6...
Great news, congrats Chris!
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Activities that build community and collaboration. (5/5)
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Consideration for our Endowed Scholars Program (large start-up package). (4/5) www.utsouthwestern.edu/education/pr...
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Faculty mentoring (grant writing workshops, chalk talks, strategy sessions, etc.). (3/5)
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A highly collaborative and supportive environment that enables innovative science. (2/5) www.utsouthwestern.edu/departments/...
Faculty search announcement 2025: Tenure-Track Assistant Professor in Microbiology at UT Southwestern. We seek candidates working in microbial pathogenesis (some preference may be given to bacterial pathogens). Come join our community! (1/5) www.utsouthwestern.edu/departments/...
Very proud to have our lab’s first work published in @cp-cellhostmicrobe.bsky.social!
In this work, we use functional metagenomics to find phage defenses from human and soil microbiomes!
Congrats to first author @luis840alberto.bsky.social !
www.cell.com/cell-host-mi...
(1/3)
Exciting news: Carla Saleh is now Chair of Virology at Pasteur! Congrats to Carla and all who will benefit from her exceptional leadership!
Finally, huge congrats to Valerie on this story, which spanned virology, genetics, cell biology, biochemistry, and mouse infections (thanks to @robertmaples.bsky.social for help with mouse work!). She defended her thesis last week and will start a postdoc with @msdiamondlab.bsky.social soon! 10/10
Thanks to the reviewers and editor Ken Cadwell for their very helpful/constructive comments that improved our paper. Their reviews and our responses are available here under the Peer Review tab: journals.plos.org/plosbiology/... 9/10
This story illustrates why we love forward genetic approaches in virology—they reveal unanticipated facets of replication. In a system where any mutation that increases early progeny could be selected, the fact that an egress-enhancing mutation emerged highlights the inefficiency of MNV egress. 8/10
We don’t know. But it could be: 1) Early cell death reduces total viral yield in the long run. Indeed, we found that WT “catches up” over a full 16 hour single cycle of infection, 2) Early progeny release induces early host immune responses, 3) K40R viruses could have transmission defects. 7/10
Does NS3-K40R suffer a fitness cost in mice—a complex environment with more selective pressure? Nope. At least not in our relatively short-term infection experiments. So why doesn’t WT virus have arginine at position 40? (Fun fact: human Norwalk virus DOES have arginine at this position.) 6/10
Instead, NS3-K40R viruses have faster egress from cells due to earlier mitochondrial disruption and cell death. In spite of this conservative amino acid change, NS3 protein containing K40R disrupted liposomes that mimic mitochondrial membranes at concentrations 10-100 fold lower than WT NS3. 5/10
She identified a mutation in the N terminal domain of NS3—K40R—that was sufficient to increase replication speed. Curiously, the mutation did not alter RNA replication or NTPase activity, two other important functions of NS3. 4/10
But we didn’t know that when Valerie started her project in 2021. To identify inefficiencies in replication, she used a forward genetic approach to enrich for MNV variants that replicate faster, by collecting the very earliest progeny. (We had IBC approval in advance!) 3/10
In 2023 our colleagues @tiffanyreeselab.bsky.social & @hanckslab.bsky.social showed MNV egress requires viral NS3, which disrupts mitochondria to induce cell lysis. Without this function of NS3, cells become bags of viruses that can’t escape. 2/10 www.nature.com/articles/s41...
