Xiangbin Ruan

Postdoc RNA-binding protein & Neural development

[Xiangbin Ruan @Cham74751558]

Thrilled to share our latest work, offering an innovative alternative for discovering RNA targets of your desired RBPs! Grateful to Zhang's lab @xczhang11 and all who contributed to its realization. Stay tuned for the imminent release of related plasmids on @Addgene

[Nature Communications @NatureComms]

A dual-deaminase method for identifying the targets of RNA-binding proteins @xczhang11 @Cham74751558 #PIESeq #RNAProteinInteraction #UnveilingRBPTargets

#BiotechNatureComms

https://t.co/4oQbyXe0fV

[Xiangbin Ruan @Cham74751558]

Does anyone by chance know where to buy this kind of Y-connector? It is for connection of commercial forceps-like electrodes to a same pole to make a tri-polar electroporation. https://t.co/yhv0m60dD6

[Michael Fischbach @mfgrp]

Your career = a finite number of weeks. Most would agree that time is precious & should be used for maximum impact, but acknowledging this and practicing it are two different things. Especially important when choosing a problem, which can impact time allocation for years. 2/53

[Veera Rajagopal  @doctorveera]

Buckle up! We're in for a wild ride today. A new @NatMetabolism paper by scientists from China adds a surprising twist to the long-known FTO GWAS story.

The FTO locus (16q12.2) is the first ever GWAS locus to be associated with obesity and even after 16 yrs now, scientists appear to be scratching their heads trying to make sense of this locus. Non-coding intronic variants within FTO strongly associate with BMI, where individuals homozygous for the top risk variant weigh ~3kg more than non-carriers (https://t.co/vh4ceXVQaQ).

Since its discovery in 2007, there have been tremendous efforts to identify the causal gene(s) at this locus. Given that the risk variants are sitting right within a gene, FTO was of course the primary suspect. How do you find out if FTO has an effect on BMI? Delete it in mice and see if the animal gains weight. And that's what scientists did and found out that Fto knockout mice were stunted and lean, and the leanness was mainly due to burning too much fat (https://t.co/DkKIGLvD0P). That's great. So FTO must be the causal gene.

But then contradicting findings appeared. If you knock out the Fto only in adipose tissue (https://t.co/W5A8JwT2Hx) or globally after the animal has grown (https://t.co/uJ69bO8A9x), the mice actually gain weight!

Amidst this confusion came an even bigger one: two landmark papers, one in Nature (https://t.co/Kq3uqKrAg1) and the other in NEJM (https://t.co/Ztqf4FTOYT), said, forget about FTO, the causal genes are located far away. The FTO locus is an enhancer that folds in the 3d space and touches the promoter of distant genes IRX3 and IRX5. And deleting Irx3 in mice resulted in weight loss.

Then scientists were like, you know, a proper experiment would be not to knock out Fto or Irx3, but to delete the homologous noncoding region in mice. So, they deleted an 82 basepair-homologous region in mice and showed that without this region, the mice don't gain weight when fed with a high-fat diet, and deleting this locus increases Irx3 and Irx4 expression (https://t.co/NFFL2OQNL8). So, the causal genes are IRX3 and IRX4 then.

And now, in the current paper, the scientists argue, you know, the most appropriate way to study the FTO locus is to recreate the exact genetic variant in mice and study the consequences.

What did they find? The exact opposite of what was found in humans. The risk allele that increased weight in humans, decreased weight in mice. Can it be because of some off-target effects of the CRISPR experiment? No. Even if you do the knock-in in an old-fashioned way, the results are the same. The weight loss is mainly via over energy expenditure via brown adipose tissue. Wait, there is another twist.

There is an interesting difference between humans and mice. Humans have brown adipose tissue only during infancy and then lose it as they grow into adults, which isn't the case in mice. The brown adipose tissue helps mainly during cold temperatures. The experiment mice are usually housed at around 20-22 degrees Celsius, which is an ambient temperature for humans but not for mice. It's substantially cooler than mice's "thermoneutral zone (29-31 degrees)".

So what happens when you repeat the experiments in what might be the mice's ambient temperature--30 degrees? All the weight loss effects that were previously seen at 20-22 degrees are now blunted. So, the FTO locus effects are strongly dependent on two things: temperature and the presence of brown adipose tissue. And it turned out, in fact, it was previously shown in humans that the FTO variant has an age-dependent effect. It lowers the body weight in infants and then increases the body weight in adults, which aligns with the current finding. (https://t.co/S7iKVj0p5d)

Overall, the current paper is an impressive work and will stand as a landmark in the long twisty road of FTO story. But above all, this paper is a remarkable example to show case the challenges behind translating mice physiology to human physiology.

https://t.co/i8IIr2bSFc

[Xiangbin Ruan @Cham74751558]

Excited to share our PIE-seq work online today! Tons of thanks to Xiaochang, for your mentoring and ongoing support! @xczhang11

[Xiaochang Zhang @xczhang11]

Glad to share that our work “PIE-seq: identifying RNA-binding protein targets by dual RNA-deaminase editing and sequencing” is online today @NatureComms. https://t.co/iCj3iqcCT8 Congratulations to Dr. Xiangbin Ruan @Cham74751558 for spearheading this project!

[Sasha Gusev @SashaGusevPosts]

A 🧵of some work from last year led by talented people in my lab and our collaborators:

[Xiangbin Ruan @Cham74751558]

@chaolinzhang Congratulations!!!👏👏👏

[Wnt publications @WntPublications]

Zbed3 Is Indispensable for Wnt Signaling Regulation of Cortical Layers Formation in Developing Brain: Wnt/β-catenin signaling plays multiple important roles during mammalian brain development, and it regulates the proliferation and differentiation of… https://t.co/b0eQjRhrk1

[The Struggling Scientists @TheStrugglingS4]

That's the holiday spirit 😂

#phdchat @PhDVoice @GSconfessional @AcademicChatter #phdlife #AcademicTwitter #academictwitter @OpenAcademics

[Cell Press @CellPressNews]

New research article from @AJHGNews: Brain-trait-associated variants impact cell-type-specific #gene regulation during neurogenesis @GeneticsSociety @jsteinlab https://t.co/GhQyNpoz08

[bioRxiv @biorxivpreprint]

Genetic studies of human-chimpanzee divergence using stem cell fusions https://t.co/Y2A38vF6au #bioRxiv

[Oded Rechavi @OdedRechavi]

“For 15 years I had 8 post docs trying to clone the gene and only the 9th succeeded!”

[Elisa Granato @Prokaryota]

Planning experiments vs Doing experiments

[Joe Pickrell @joe_pickrell]

"The genetic basis of tail-loss evolution in humans and apes" https://t.co/0eUKQzckNn

[Patrick Hsu @pdhsu]

Paul Nurse, who won a Nobel for his work on the cell cycle, calls for more daring theory in biology and criticizes current trends in large scale data generation. We probably need to reimagine the Discussion section of papers! https://t.co/R9XhI1Iy76

[Xiangbin Ruan @Cham74751558]

@Sobreira_DR 👏👏👏 Congrats！

[Chris Miller @chrisamiller]

In our new preprint, we show that problems with the GRCh38 reference can cause in mutations in U2AF1 (a common cancer driver gene) to be missed. This is a big problem if you're looking at blood cancers or studying the spliceosome (1/6)
https://t.co/M7myTyRRAb

[Society for Neuroscience (SfN) @SfNtweets]

Congratulations to Christine Petit & Christopher A. Walsh, winners of the 2021 Gruber Neuroscience Prize for Pioneering Discoveries Regarding the Genetic & Molecular Mechanisms Behind Neurodevelopmental Hereditary Disorders. Read more about the laureates. https://t.co/e6tcKR9F3T

[Shane Liddelow 🍊 @LiddelowSA]

I was expecting to see 'we hope you don't notice cluster 4 is driven by a single donor with excess mitochondrial counts'

[Xiangbin Ruan @Cham74751558]

My PhD work is finally online
Zbed3 Is Indispensable for Wnt Signaling Regulation of Cortical Layers Formation in Developing Brain https://t.co/DNeM2yEUVA