Assistant Professor of Mol Bio at UT Southwestern, switching diseased molecular networks back to health. We typically study serendipitous distractions...
(1/6)
@meladenosine
and I are thrilled to announce that the Sanders Lab will launch in November 2023 at UT Southwestern (primary,
@UtsWcand
; secondary,
@UTSWMolBiol
and
@UTSWBrain
). We will pursue curiosity-driven science related to RNA-protein assemblies and diseases of aging!
In today's issue of Cell, we (Brangwynne lab) have back-to-back papers, which use novel optogenetic methods to examine contributing factors () and functional consequences () of phase separation in the nuclei of living cells!
Two new papers probe the transition between protein clustering and phase separation: (1) in vitro (); (2) in cells () ....no, nothing in biology is (likely) as simple as liquid-liquid phase separation (LLPS)!
We have a paper out today. Like me, you may be distracted by...A LIFE-ALTERING PANDEMIC! Read once this terrifying time passes? Don't worry: we can return to hexanediol jokes and arguing about phase separation minutiae soon. Be safe and take care of your mental health! <3
remember when you first learned that primary cilia were a thing? and you thought the person telling you was screwing with you? and then you realized that you knew nothing about cell biology? that was a nice moment.
This (revised) pre-print from
@arjunrajlab
and colleagues is just marvelous! Enormous implications for how I (we?) think about kinetics of mRNA processing/export via subnuclear compartmentalization.
@aisha_dickerson
Disagree strongly. Annoys me when people refer to me by dr last name or professor last name. Seems like they don’t understand how academia works.
@drama_science
I first heard multiple accounts of his predatory behavior five years ago (!!!), despite being unaffiliated with his institution or field. Remarkable that his institutions took so long to act. Well, better than no action at all.
First Sanders Lab meeting. The most exciting one: discussion of database organization. Very metal! Next on agenda? Cure the diseases. First up: all of them. All. Guessing…boron (?)…is the answer? Certainly boron. Not manganese, that’s for sure. Still on my element shit list.
Super-thrilled for my advisor, Cliff Brangwynne (
@brangwynnelab
), who together with
@HymanLab
won the Breakthrough Prize for their work on biomolecular phase transitions! Very much deserved and incredibly exciting for the field!
@Nature
hard to imagine why PIs who assign specific projects to trainees have difficulty recruiting ambitious post-docs who want to chart their own paths...
I have a going away party tomorrow to celebrate the start of a new adventure with
@meladenosine
at UT Southwestern. Overwhelmed by the idea of leaving such an amazing group of people behind in the
@brangwynnelab
. I will miss everyone dearly! Take care of my 10k cell lines :)
Just read latest pre-print from
@pelkmanslab
and
@scottbscience
on RNA feedback/homeostasis. What a great (and rare?) example of using big data to inform hypothesis-driven experiments that uncover simple principles of cell biology. Highly recommended!
The formatted (!) version of our paper on COVID-19-associated multinucleated cells ("syncytia") is now out in eLife (). A thread on some of the findings that interest me most (1/7)
Congrats to some of my fave neurodegen labs (Gitler, Petrucelli,
@ShorterLab
,
@schmidt_lab
) for their clever "nuclei sorting"-informed work on how TDP43 loss drives ALS: ...Accompanying paper uses KD to reach similar conclusions:
Our lab space has unexpectedly become a hot spot to shoot promo commercials for UT Southwestern. Have a passion for science AND want to add a credit to your IMDB profile? Join the Sanders Lab. Where stars are born!
Exciting news! I've accepted a job offer at
@RockefellerUniv
The Bonilla lab is opening this fall and is hiring at all levels! Interested in exploring RNA structure-function using
#cryoEM
, biophysics, computational tools, etc? Interested in viral RNAs? Join us in beautiful NYC!
@AdrianoAguzzi
Way too many cynical takes on academia on Twitter. Glad I wasn’t exposed to all the complaining as a young graduate student. Yeah, I could get paid more elsewhere but in my opinion, enjoying life and scraping by>>>accruing retirement cash, waiting for happiness that never comes.
After a crazy four-month sprint, finally submitted my first paper as a post-doc! Thanks to
@DNAmyStrom
,
@danielswlee
, and
@SuperSciJew
for helping drag its corpse over the finish line! Note to self: don't plan another three-way co-submission anytime soon.
This is a really cool paper. Might non-enzymatic polyphosphorylation of histidine and lysine residues play a role in nuclear speckle organization (and electrostatic coacervation more broadly)?
Fantastic new study on how RNA-binding prevents TDP43 aggregation. Further challenges idea that stress granules directly nucleate TDP pathology in FTD-ALS:
I'm happy to share our pre-print on the role of cholesterol in SARS-CoV-2 infection and multinucleated syncytium formation. See Cliff's thread for a nice summary of the work! Now back to nuclear speckles :)
(1/n) Thrilled to release our contribution to understanding the molecular mechanisms of SARS-CoV-2 infectivity, combining cell biology, biophysics, bioinformatics, virology, & clinical pathology, to elucidate the critical membrane-membrane fusion event...
12-hours til Texas-bound. Still in lab. Luckily I have an additional 12-hours buffer zone once I arrive In Dallas before I officially start. Moving. Is like. Stressful.
Today in my life: "Yay, I'm cited!"
...
"Wait....what for?"
... (scrolls) ...
"No statistical methods were used to predetermine sample sizes, but our sample sizes are similar to those reported in previous publications (Sanders et al., 2014)"
"...oh, I see. For incompetence"
Today I learned that the more you know about a topic, the more difficult it is to communicate your scientific rationale. Well this certainly explains a lot about academia.
Important paper for stress granule community! An artifact in commonly shared G3BP constructs underlies misconception that G3BP phospho-S149 regulates SG condensation. Kudos to Kedersha/Panas for publishing work that refuted parts of their former paper:
A balanced perspective in Science, highlighting (appropriate) caution toward qualitative "everything is phase separation" papers. Some kind words from Mike Rosen on our paper in Cell last year too!
Getting paper
#2
from postdoc ready (maybe on biorxiv in a week?). Here's something from the cutting room floor...no, nothing to do with phase separation. New genre.
(6/6) Finally, to those on the job market this year: please message me if you would like someone to demystify the experience of applying to R1 med schools. Promise an unvarnished take + sharing of potentially helpful documents! Need to pay forward what was given to me last year!
We have received requests for PDFs of paper since it is not open access. Below is a 50-day pass to download the paper, which Cell/Elsevier kindly provides for sharing on social media:
I know many are upset that I don't tweet as much about phase separation papers as I used to.
@ShorterLab
was just crushing me--it was embarrassing. But this one is important. Avoiding sticky phases in shelf-stable Pad Thai sauce. Big if true:
This is a phenomenal iNeuron screen (re: hits that up tau seeding). Implicates membrane homeostasis, particularly receptor recycling, lipid metabolism, and vesicle acidification. Note: ~1050 genes screened (5% NonTarget ctrl; Table6, I buy top 80 as real).
Thanks cliff! Can’t imagine a better environment in which to thrive than your lab. Somehow my gut instinct to bet on some salad dressing dude paid off royally! (For those who don’t know me: this is a compliment)
Josh is a brilliant young mind—one of the few individuals I’ve met who is both a remarkable physicist and great cell biologist. Highly endorse applying to his new lab at Baylor! Get in on the ground floor of an ascendant research program!
Excited to confirm that I am starting
@RibackLab
joining the department of MCB
@BCMHouston
with support from
@CPRITTexas
! We'll be hiring, so if you're interested in bridging the biology and physics of Biological Condensates, please get in touch!
When I entered field (2010), AB*56 was already a joke. No one ever followed up b/c it was not reproducible. Beware of equating citations with continued impact. Sadly, highly cited papers continue to be cited out of laziness (“cite an oligomer paper here”):
Remember when I used to post videos of strange microscopy phenomenology that will of course never be published? Let's start doing that again. Here is an oligomerized IDR that likes nucleolar FC (PolI txn sites) and surface of vesicles but not speckles. Screw you speckles!
@StearnsLab
the faster we can test and discard wrong ideas; vs test and support (likely) correct ideas, the better. pre-prints are a fantastic band-aid for the sludge-y bureaucracy of modern peer review.
A very kind write-up on our recent Cell paper from post-doc David Bing (Mike Levine lab)! Not going to argue with "tortured scientist demeanor", but was there really need to leak my darkest secret? Yes, I have a Psychology degree--I was young and foolish! 😆
How can the physics that govern a lava lamp’s behavior revolutionize our understanding of cellular and molecular biology? Check out our most recent review on the work of CBE’s David Sanders to learn more: (1/3)
#princeton
#chemical
#engineering
Advice to future postdocs on job market. Don't trust ChatGPT to write your thank you emails in the style of Kanye west...particularly to Nobel Prize winners. Why? ChatGPT told me it's less than ideal:
@arjunrajlab
God I can’t imagine where I’d be if science Twitter informed my initial working model for what scientists think about science. This place is a cynical hellhole. And all the things I really love about science are routinely denigrated here. So much groupthink.
(2/6) Please reach out if your favorite papers start w/ a mistake, following a serendipitous observation into the unknown. We will be hiring fearless iconoclasts at all levels! For more, see
Cool study in this week's Science on the role of the endoplasmic reticulum in regulating P-Body formation and fission--a bit of stress granules in there too for the fans:
New Don Cleveland paper adds more compelling data to counter popular hypothesis that stress granules are upstream from TDP43 pathology in neurodegenerative disease:
Stan is one of the few great iconoclasts of academia. He and Jonathan weissman, along with their brilliant trainees, took a seemingly intractable problem and broke it down into remarkably simple principles with intimidatingly elegant experiment design.
"I am one of those genuinely lucky scientists who was handed a special opportunity to work on such a problem – that of prions."
Stanley Prusiner was awarded the 1997 medicine prize "for his discovery of Prions - a new biological principle of infection".
Brangwynne Lab introduces new optogenetic technique ("corelets") to determine complete phase diagrams for protein complexes in living cells. Reduced diffusion allows LLPS of proteins at low concentrations. Could this occur at genomic loci to drive txn?
Great idea, Rohit. If sticking to the 2018-2020 window and had to choose just one you missed, it would be the quantitative masterpiece on tight junction formation from
@Honigmann_Lab
#QuantitativeAndRigorousPS
#QuantitativeAndRigorousPS
papers created in response to pings asking that I list papers that represent "quantitative & rigorous work" in the field of intracellular phase transitions. I indicated there were numerous, but challenge seen, challenge accepted 👇🏿
Excellent, carefully performed study on amino acid composition and charge patterning as it pertains to partitioning of low complexity domains into speckles and nucleoli:
New preprint from us!
mRNAs act as chaperones for IDRs.
mRNAs often bind to IDRs. This changes their conformational ensembles to drive protein complex assembly, and controls protein activity.
Thank you
@VickyLuo0223
!
@PappulabWashU
Isn’t this nice? Now that trump is gone, we can get back to arguing about things that matter. Like rationale for science news division’s puff pieces/click-bait. It’s a damn good day!
Two papers (Alberti/Hyman, Gladfelter) out today in Science on the role of RNA in regulating phase separation [nice result from Alberti showing that RNAse injection drives RBP LLPS]:
Remarkable work on single cell transcriptome of tau aggregate-containing neurons from Alzheimer's patients. Downregulation of ribosomal biogenesis factors, splicing proteins previously implicated in AD (e.g. SNRNP70/u1-70K). Late-onset risk factors seen...
This is Jeffy. She just turned 13. She has 100s of toys...most hoarded under the bed. But not this little monster thing. I thought it might be smell-based. But it accidentally went through the wash multiple times. And obsession increased. Anyway, Jeffy wanted to tell Twitter.
@YSPTSPS
While this may be the most rigorous tweet yet regarding the high intrinsic value of doing science in 2019, it improves only incrementally on past tweets addressing similar concepts. The work would be more suitable for a field-specific social media platform e.g. ResearchGate.
I dream of one day completing a paper submission cycle without succumbing to the sleep deprived madness that produces such horrid prose. I apologize immensely for my sin (sins?) against the English language.
Has anyone read a paper that relies heavily on the "proximity ligation assay" that does not appear to be covering for shoddy science? Not talking about APEX/TurboID/etc....
Science has entered into an arms race w/ Cell to see who can publish the most phase separation papers. Two new ones: one on a potential role for LLPS in synaptic organization ()and another argues for its role in innate immunity ()