Community Newsletter: Lab Collaborations, Interneuron Network Expansion, DDX3X | Spectrum

Not all debates on Twitter become controversial. Case in point: This week, a troop of scientists used the platform to call for greater collaboration between labs that work with non-human primates and those that work with rodents or humans.

“The challenge is to get the vast majority of neuroscientists, who conduct experiments on rodents or humans, to recognize the need NHP research to bridge the gap between these phylogenetic levels,” tweeted Douglas Crawfordprofessor of neuroscience at York University in Toronto, Canada.

The challenge is to get the vast majority of neuroscientists, who conduct experiments in rodents or humans, to recognize the need for NHP research to bridge the gap between these phylogenetic levels. Or even acknowledge the gap.

— Doug Crawford (@J_D_Crawford) June 27, 2022

This task would be easier if “the PSN people were better at articulate key areas for which NHPs are essential,” replied Anne Churchland, professor of neurobiology at the University of California, Los Angeles. Too many people, she continued, justify PSN’s work simply by “claiming that mice are ‘dumb, blind, and not like us’.”

I’ve done this a lot (at NIH, etc.). My job would be easier if the NHP people knew how to better articulate the key areas where NHPs are needed. Honestly, this might seem like a tough bunch to negotiate as many justify PSNs by claiming that mice are “dumb, blind and not like us”.

— Anne Churchland (@anne_churchland) June 27, 2022

“Shit on mice is counterproductive because The PSN is the minority…by a lot,” tweeted Cory Miller, associate professor of psychology at the University of California, San Diego, who works with marmosets and wrote that he thinks NHP work requires “better integration with the mouse community to survive.”

Anne, IMHO NHP work needs better integration with the mouse community to survive. That the mice are “stupid/blind/etc.” is largely inconsequential. Shitting on mice is counter-productive because PSNs are in the minority… by a LOT! Closing this gap is a priority for SimCo w @MIcheleABasso1

— Cory Miller (@CoryMillerMarmo) June 28, 2022

Such integration would only help both communities, others have stepped in.

“I have seen many mouse papers that suggest they have discovered something new this has actually been well studied in monkeys,” tweeted Michele Basso, professor of neuroscience at the University of California, Los Angeles. “Let’s work together !!”

It goes both ways – I’ve seen a lot of articles on mice that suggest they’ve discovered something new that has actually been well studied in monkeys – the OKR is one example. Let’s work together !!

— Dr. Michele A. Basso (@MIcheleABasso1) June 28, 2022

“Same with humans and PSNsCrawford commented. “Human neuroscience offers a more holistic view, like looking at Earth from space, while NHP neurophysis is like getting down to the ground where people are and shaking hands.”

Same with humans and PSNs. Having done both for many years, I find that human neuroscience offers a more holistic view, like looking at the earth from space, while the NHP neurophysis is like getting down to the ground where people are and shaking hands hand.

— Doug Crawford (@J_D_Crawford) June 28, 2022

More cross-species comparisons popped up on Twitter in the feed of Moritz Helmstadterprofessor of neuroscience at the Max Planck Institute for Brain Research in Frankfurt, Germany, who asked “What makes us human, at the level of the neural network? His recent discovery offers an answer: a 10-fold increase in interneuron-to-interneuron networks in the human brain compared to the mouse brain.

What makes us human, at the neural network level? We found a dramatic (10-fold) expansion of interneuron-to-interneuron networks in the human brain compared to the mouse: @ScienceMagazine @MpiBrain @maxplanckpress https://t.co/eRYZyDyKVz pic.twitter.com/BmpwkF5922

—Moritz Helmstädter ???????? (@mh_lab) June 24, 2022

Helmstaeder went on to explain how he and his collaborators came to this conclusion in more than 25 additional tweets – earning thousands of likes, hundreds of retweets and dozens of quote tweets.

“Thank you for a great collaboration“, tweeted the co-investigator Hanno Meyerneuroscientist and neurosurgeon at the Technical University of Munich in Germany.

Thanks @mh_lab for an excellent collaboration! Very proud to have participated in this study and to have been able to allow such an amazing study @NCH_TUM @TU_Muenchen. Clinical #neuroscience will soon realize the potential of this methodology& #neurosurgery will be the key to its future development and application https://t.co/uaeCD9H32s

— Hanno Meyer (@hsmeyer) June 26, 2022

“Fascinating #brainevolution study“, tweeted Christopher WalshBullard Professor of Pediatrics and Neurology at Harvard University.

Fascinating study of #brainevolution https://t.co/PrK8N1HBMd

—ChrisAWalsh (@ChrisAWalsh1) June 24, 2022

Future work on “possible pathological alterations of the human cortex” should consider “alterations of interneuron-to-interneuron connectivity“, tweeted Cedric Boeckxresearch professor in linguistics at the University of Barcelona in Spain.

“Alterations in interneuron-interneuron connectivity should become an object of study in the context of possible pathological alterations in the human cortex”
Nice study of @mh_lab et al. on the evolution of the complex inhibitory network ????. Summary ???? @ScienceMagazine paper link???? https://t.co/NRs2cr6ZtR

— Cedric Boeckx (@cedricboeckx) June 24, 2022

And DDX3X, a gene linked to autism and cancer, featured in several other popular tweets. Matthew Hurleshead of human genetics at the Wellcome Sanger Institute in Hinxton, UK, shared a thread about his new preprint that maps the functional effects of all known variants of the gene.

Really excited to present a ????on our new preprint https://t.co/vN0OEGltBn, using saturation mutagenesis to determine the functional effect of >12,500 variants, including all SNVs, in the DDX3X gene. Work led by @HongkeeTLizzie Radford and @GeretySebastian.

— Matt Hurles (@mehurles) June 20, 2022

After introducing the variants into HAP1 cells and tracking their relative abundance over 21 days, the team grouped 3,432 variants into three categories: fast-depleting, slow-depleting, and enriched.

The results are “very informative“for neurodevelopmental conditions and cancer, Hurles summarized, even if they come from a cell type of little relevance to either condition, “suggesting that, for DDX3X, pathogenetic variation is intrinsic to the proteins”.

“Nice analysis” was how Claire Turnbullprofessor of cancer translational genetics at the Institute of Cancer Research in London, UK, described him as a tweet quote. “Beautifully exemplifies the power to advance variant interpretation,” she added.

“Great job,” wrote Veera Rajagopal, a scientist at biotech company Regeneron Pharmaceuticals in New York.

Debra Silverassociate professor of molecular genetics at Duke University in Durham, North Carolina, has published a paper on his independent work on the mechanisms of DDX3X mutations in mice – findings that Spectrum covered last month. “We profile translation early in neurogenesis highlighting the importance of RNA regulation,” Silver wrote.

Excited our study is over! Led by a super talent @mariahhoye we uncover new mechanisms by which Ddx3x mutations impair brain development and cause @ddx3x syndrome. We profile translation early in neurogenesis highlighting the importance of RNA 1/ regulation.https://t.co/N4mgjVSpOD

— Debby Silver (@TheSilverLab) June 30, 2022

“Big story by the Debbie Silver Lab! wrote Joseph Glenonprofessor of neuroscience at the University of California, San Diego, who served as editor for the study for the review eLife.

That’s it for this week’s Community Newsletter! If you have any suggestions for interesting social posts you’ve seen in autism research, feel free to email[email protected].

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