Jordan Meier
@doc_jlmeier
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Chemical biologist, basketball aficionado, proud homebody. My tweets are my own.
MD via CA via IA
Joined June 2014
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Finally a dose of resveratrol sufficient to activate SIRT1.
The streets of Levira, Portugal were flooded with red wine after a distillery’s 2.2 million liter tanks burst.
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This is what you get without an HOA.
We have one bench in our lab that isn’t governed by the HOA and this is what we get as a neighbor.
This is what you get without an HOA.
We have one place in our neighborhood that isn’t governed by the HOA and this is what we get as a neighbor.
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Nature research paper: Uncovering new families and folds in the natural protein universe
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I'm synthesizing a molecule a week in 2023. Alkaloids, polyketides, or anything people highly recommend. I'll keep adjusting the list. Start on Monday, done by Sunday. Might make lowkey TikToks of prep TLCs. If you want to chem along, current list is here:
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Most PI's are unhappy.
So, I've spent 20 hours studying Dmitri Mendeleev's life and works over 3 months.
What I found?
Mendeleev's Happiness Formula for PI's Living In the Hellscape of 19th Century Russia:
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Many folks are mocking me saying it is not feasible to synthesize one complex molecule a week.
Sharing my morning regimen in hope it helps you achieve your own 2023 goals. 🥰
I'm synthesizing a molecule a week in 2023. Alkaloids, polyketides, or anything people highly recommend. I'll keep adjusting the list. Start on Monday, done by Sunday. Might make lowkey TikToks of prep TLCs. If you want to chem along, current list is here:
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I was experimenting with DALL-E-3 and asked for an image of a scientist mouth pipetting. I don't think I have laughed so hard all weekend....🤣🤣
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2003:
Paper
Figures
SI
Letter to Editor
Submit
2023:
Paper
Figures
SI
Letter to Editor
Biorender clearance
Employee Invention Report
Repository data upload
Author emails
Publishing checklist
Journal publishing agreement
Reviewers list
PDF check
Biorxiv
Tweetatorial
Submit
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HOLY COW THE LAB IS TEN YEARS OLD!!
So grateful for my colleagues, co-workers, and most of all for the opportunity to pursue significant science
@NCIResearchCtr
. Special thanks to my family and Meier lab alums.
Photos charting a decade of progress in and outside the lab.
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New nomenclature for graduate students just dropped
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A prerequisite for acetyl-CoA sensor design is the identification of scaffolds that differentiate it from structurally similar metabolites. How can we identify proteins with these molecular recognition capabilities? Short answer: chemoproteomics! A 🧵:
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🚨Fully funded postdoc opportunity in the Meier lab!!🚨
Great projects studying the metabolism-epigenetics interface in cancer 🍲🧪, RNA modifying enzymes🧬, and an AWESOME team of colleagues.👩🔬👨🔬.
Please RT!
#metabolism
#acetylation
#chemicalbiology
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A genetically-encoded fluorescent biosensor for visualization of acetyl-CoA in live cells
Clever insertion of cpGFP into loop of a GNAT provides a tool the field has been craving for years.
Happy New Year to the
@therealdiehllab
@uofupharmacy
!! 🎉🎉🥳
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This weekend marks my oldest daughter’s 11th birthday.
It also marks my third year of sobriety.
Thoughts on a perfect Maryland afternoon. 🧵
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Wow! Beautiful application of orthogonal proximity proteomics methods by
@aliceyting
lab
Dynamic mapping of proteome trafficking within and between living cells by TransitID
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Banner day for chemical biology & proteomics on
@biorxivpreprint
this Saturday AM.
Genuinely cannot ever remember seeing so many interesting papers posted near simultaneously.
Going to need an entire pot of ☕️ to read through. Check them out! 👇
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The final version of our acetyl-CoA sensor work led by
@whit_lieberman
and
@zachabrown_
now out
@J_A_C_S
!
New since the preprint: quantification from cellular samples (w/
@mzspectrum
) and a PANK-based Nluc reporter. Postbac-driven. 👩🔬👨🔬💪Check it out!!
A prerequisite for acetyl-CoA sensor design is the identification of scaffolds that differentiate it from structurally similar metabolites. How can we identify proteins with these molecular recognition capabilities? Short answer: chemoproteomics! A 🧵:
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Recently heard one of my favorite professors Mark Kearley, formerly of Creighton University, currently at Florida State, is retiring soon. He had a huge impact on my life.
In honor of Kearley and the Thanksgiving spirit, here is a story I told my daughter tonight.
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New work from the group led by stellar postdoc
@DrKnance
. We find base hyperacetylation dampens immune activation and alters the interactome of synthetic mRNA. Potentially useful for tuning the properties of functional nucleic acids. Congrats Kellie & co!
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Wow! "Designed Endocytosis-Triggering Proteins Mediate Targeted Degradation and Amplify Signaling"
Baker x Bertozzi: the biggest crossover since Infinity War
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Being a popular PI means more meetings with imperial bureaucrats.
Being in the spotlight drains your energy for experiments when you need to chop wood to survive the winter.
Get grant money, then disappear into your lab/hovel forever = Happiness
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You really can have it all.
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Be unconventional and daring:
-Have 16 siblings.
-Present your research at seedy taverns.
-Engage in interdisciplinary collaborations with Dostoevsky.
-Challenge established theories, and the Czar.
-Attend conferences on the Trans-Siberian Railway
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Forget trying to be the most cited chemist in your cholera-ridden village.
"Focus on the quality of your research first. See if that doesn't cover most of it."
Fame = Distractions from avoiding dysentery
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New from the lab! We explored covalent ligand screening and chemoproteomics as a new approach to identify synthetic lethalities in HLRCC, a cancer syndrome driven by the electrophilic oncometabolite fumarate.
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Embrace the chaos, like Mendeleev did after his family glass factory burned down and his father went blind.
"I saw in a dream a table where all elements fell into place as required. Awakening, I immediately wrote it down on a piece of birch bark. Only in one place did a
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Can a cake degrade BRD4?
Chemist Josh Smalley is competing in The Great British Bake Off this year. He is a postdoctoral researcher at the University of Leicester, where he cooks up small-molecule probes and proteolysis-targeting chimeras (PROTACs). Read more:
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WOW! Evidence the nuclear CoA metabolite pool is distinct, dynamic, and feeds specific PTMs. Landmark study by
@trefely
@mzspectrum
@WellenLab
and team. 💪🥼🏆
@PennMedicine
@templemedschool
#Metabolism
#Epigenetics
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Delighted to share this study led by
@elaine_zhou
at
@MarmorsteinLab
@PennMedicine
. The first structure of a eukaryotic RNA acetyltransferase provides insights into substrate binding, catalysis, and mutations useful for exploring Nat10 as a drug target.
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Tell everyone you're taking a sabbatical.
"This is what I do when I need to focus on my research and not dying of consumption. It's great, because you can just say, 'Oh, I'm sorry. I'm on sabbatical.'"
1. It's a nice way to avoid the terror of existence.
2. People think you're
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The importance of nomenclature:
N1-methylpseudouridine, the mod used in COVID vaccines, wasn't tested in Kariko & Weissman Immunity 2005.
However, the patent that followed makes reference to "1-methylpseudouridine" among a long list of modified bases as a potential embodiment.
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I wish the people somehow taking this as an attack on grad student salaries would summon even half of that energy to lobbying Congress to increase science funding. That lack of growth is the root cause of a lot of the angst in this thread.
How much does a graduate student cost per year?
Salary: $35,793
Benefits + Tuition: $26,463
Supplies: $12,000
Travel: $3,000
Overhead: $42,491
Total: $119,747
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"THIS NEW WORKOUT PROTACS MY BRD4 UNTIL MY BODY CRISPRS ITSELF."
Bryan Johnson spends $2 million a year to be 18 years old again.
In 2021, he reduced his epigenetic age by 5.1 years in 7 months (a world record)
His 13-steps for a long healthy life:
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Cryo-EM of nucleosome-bound EP300!! Structural insights into the role of bromodomain and epigenetic propagation of histone acetylation.
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My Dad always said “Do the most you can, not the least you can.” Happy Father’s Day to my pops and all the other Fathers out there doing the most.
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Happy Holidays from the Meier Lab!
May your notebooks always be full. May your pipettes ever be calibrated. And may you be finished collecting data a half hour before the LC knows it's clogged.
Wishing you fellowship & scientific breakthroughs in 2024.
(❤️ this group!)
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Excited to share our latest tool for illuminating "dark matter" in the world of acetylation! Out now in
@J_A_C_S
: A sequencing reaction for single nucleotide resolution detection of N4-acetylcytidine in RNA.
#MeierLab
#RNA
#acetylation
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Most publish-or-perish advice is bourgeois nonsense.
"I'm not a workaholic, I only publish papers 2 times a year. When it's a breakthrough & when I'm trying to avoid freezing to death.”
It's ok to have brief moments of joy before the despair sets in.
It's ok to take breaks to
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I routinely make over six figures for a single manuscript.
Can confirm. I have published over 200 scientific publications and by now my annual royalties have reached six figures. Last year I made $000000 for my lab.
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These are now $800 per bag at VWR
Is there a more clever use of those big paper clips than this? Taguchi lab, Tokyo Tech.
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"Indeed, our work more generally raises the possibility of posttranslational modification in trans, the delivery of a PTM through a small molecule intermediary."
Wild little mechanism here for a phenotypic screening hit.
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Excited to share the lab's latest pre-print "Paralogue-specific degradation of the lysine acetyltransferase EP300."
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Fathers Day meets post-GRC recovery. Happy Pops Day to all who celebrate!
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Chemical biology finally has a home in the
@AmerChemSociety
! Small name change = big deal. Wonderful news from
#ACSSpring2024
Thrilled that
#ACSSpring2024
Council voted to approve BIOL
@ACS_DivBioChem
's name change request to *Biochemistry and Chemical Biology*! 90% of BIOL members voted that this better represents them & we hope to provide a home for even more scientists
@AmerChemSociety
- More soon!
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Degrading BRD4
What are you convinced people are pretending to enjoy?
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This is how you label things to not be discarded at group cleanup. 🧬 🧪
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Are you a chemical biologist who is having a baby?! Here are some nice
#chembiol
names for your child!
Maldi
Protac
Azide
Ester
Phage
MOFO
Bruker
Glicknack
Edman
Are you a computational chemist who is having a baby?! Here are some nice
#compchem
names for your child!
Amber
Serine
Byte
LINCS
Queue
Ewald
Particle-Mesh
Convergence
Integrator
omega-B97x-D
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"It just doesn't matter! It just doesn't matter!"
PIs often worry about dumb stuff like awards, grants and not being executed by the Czar's police.
Think less of your ego.
Remember: you and your research will be dust and oblivion soon.
Now go do science that briefly dulls the
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Be like Mendeleev, and start performing your own groundbreaking research in the face of our futile existence.
You’ll find my best secrets by reading and citing my papers:
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Important reminder: follow-up and validation of chemoproteomic hits is the real battle.
From a recent
@Nature
article using a metformin photoprobe to gain new insights into this widely used drug:
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So happy to see Meier Lab postbacs Courtney Link, Sam Nance, and Whitney Lieberman representing at
#ASBMB2022
!!
Class of 2020 grads learned to lab in a pandemic, made a huge impact, now (re)mastering the art of in-person.
The future of science and medicine is bright! 👩⚕️👩🔬👩🔬😎
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Massive study from Pfizer reporting a potent chemical series targeting MYST-family lysine acetyltransferases. Promising pre-clinical efficacy in ER+ and KAT6-amplified breast cancer. Another point on the epigenetic drug discovery scoreboard!
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If you ❤️❤️❤️ thermodynamically activated metabolites check out this gem in
@JACS_Au
from
@ChristianAOlsen
lab.
Elegant chemical biology to study thioester reactivity, hard
#s
for succinylation, new insights into TCEP as a nucleophile. 💯 Will cite!
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Not sure about the new Acknowledgements format but going to give it a try
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Not the Northern Lights we expected visiting Iceland! But every scientist knows when it is time to pivot.
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@KRHornberger
I was at a dinner once with a chemist who made a key contribution to a drug. Another scientist at dinner listened quietly then said, "I took that drug, it saved my life. Can I buy you a bottle of wine?"
#LifeGoals
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New paper! Comparative analysis of drug-like EP300/CREBBP inhibitors with
@DibbleLab
Summary of a short & sweet study 👇
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Interesting paper from
@HKU_Chemistry
demonstrates N-acryloylindoles as kinetically-optimized electrophiles for profiling cysteine reactivity in living cells.
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Good move. Everybody knows that recruiting 13 postdocs is unlucky.
My lab is hiring 12
#postdocs
for 12 projects.
Requirement:
#passion
& strong
#publication
record
CV to tsmoon7
@gmail
.com
Not reviewing random applications that do not fit.
Please spread the AD. Please Retweet.
Thanks!
@EngBioRC
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I always counsel trainees to not write pun titles that will end up on PubMed and their CV forever. But I love this one:
"Friend or foe-maldehyde"
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Editing the acetylome!
Beautiful paper from Jin group
@DOMSinaiNYC
demonstrating re-targeting of the endogenous acetylation machinery to modify mutant p53.
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Electrifying seminar by
@DanNomura
who shared tales of proximity-induced pharmacology and enjoyed a bit of trolling, degrading BRD4 with six different scaffolds on a single slide.
A record that will not soon be broken. Well done sir! 🫡
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This is what happens when you take your lab notebooks home.
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Final Thought:
Some peasants said Mendeleev was an difficult person.
There were allegations of him engaging in occult practices, but that was a common smear against scientists.
Mendeleev said: "People say I'm unstable and morbid. Of course I am, I have seen beyond the veil
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"It's hard to invent the periodic table. It's hard to be anything in this dark age of superstition and oppression. It's hard to just be."
Pioneering research is hard.
A mediocre life of serfdom is so much harder.
Dare to dream.
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Mendeleev faced constant rejection as a scientist and human being.
"The scientific community did not accept the Periodic Law at once, likely because they were drunk on vodka, as were we all.”
1. Groundbreaking ideas often rejected.
2. Don't seek validation from the cruel
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Catching up on my tweets: Meier lab celebrated two amazing
@NCIResearchCtr
postbacs moving on to their next steps last week:
@Courtney_Link18
(UVA Medicine) and Sam Nance (NSF GFRP headed to Carnegie Mellon Biology).
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Few things offend my Midwestern sensibilities like a Maryland snow day (pictured)
What if, hear me out, they wait to see if it snows prior to closing schools? If it does snow and the roads are bad then you close them.
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Local Scientists Faith In Social Media Restored After Tweet Mocking Discredited Nutriceutical Does Numbers
Finally a dose of resveratrol sufficient to activate SIRT1.
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Delighted to share our recent review 'Cytidine Acetylation Across the Tree of Life,' out now in Accounts of Chemical Research.
We detail this modification's history, chemistry to discover & study it, and our group's current perspective on the field.
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Fluorophosphonate-based chemoproteomics yields a hydroxy fatty acid biosynthetic enzyme. From
@alansaghatelian
group in
@Nature
.
The perfect ABPP probe applied to the perfect system enables a new discovery. FP still got it!
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Nice strategy from Shao Yao's group uses N-terminal modification chemistry to internal lysines via ligand-directed targeting. Have always loved these mechanisms since first reading about the OPA scaffold in mid-2000's
@kevansf
lab studies.
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"New insights into the pathophysiology of methylmalonic acidemia" from Venditti lab
@NIH
@genome_gov
.
Beautiful review highlights unanswered questions, and new roles for non-enzymatic acylation in MMA. And a chemical biology prospective. 🙌 Great job Pam & Chuck!
New 'Accepted Article'
New insights into the pathophysiology of methylmalonic acidemia
PamelaSara E. Head, Jordan L. Meier, and Charles P. Venditti
#MMA
#OrganicAcidemias
#NIH
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Narrowed down the mechanism to autophagy, the UPR, the integrated stress response, metal homeostasis, TLR signaling, complex I activation/inactivation, mTOR, or ferroptosis.
But it is probably ROS.
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Hungry hungry histones:
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Wonderful visit to
@DukeChemistry
! Great sharing science with old and new friends and soooo much RNA.
Thanks to my hosts
@hargrovelab
@DerbyLabDuke
and all the students and faculty who took time to meet.
@BoyceLab
@MeyerLabDuke
@TheHornerLab
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When I tell my lab I have an idea to study another modification.
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Now published at ACS Chem Biol!
A nice Easter Egg in the SI: chiral separation and VCD-based stereochemical determination of CPI-1612 analogues by our colleagues
@ncats_nih_gov
Thanks our co-authors
@DibbleLab
& reviewers who took time to help! 🙌🙌
New paper! Comparative analysis of drug-like EP300/CREBBP inhibitors with
@DibbleLab
Summary of a short & sweet study 👇
1/n
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Made it to Dundee with some absolutely stunning views in Edinburgh and along the coast on the way up. Excited to represent the “TPD-curious” faction at this week’s
@UoDCeTPD
meeting!
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LOOK AT THIS AMAZING GROUP!!! THE FUTURE FOR
@ACS_DivBioChem
IS BRIGHT!
Congratulations to our newly elected 2024
#ACSDBC
Executive Committee members!
@jschneek
,
@barb_golden
,
@ThomasJMagliery
,
@Siecasso
,
@hargrovelab
,
@DikiyChelovek
,
@bradylabupenn
,
@SmithLabUMBC
,
@annvalentine
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Lactoyl-CoA giveaway! We made more than we need and are happy to ship out to enable science.
No MTA just DM me with FedEx #/address for a 2 mg aliquot.
Otherwise I give it all to
@mzspectrum
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Harry Gray is a TREASURE. Work on science that excites you. That you can't stop thinking about. Not all projects are like this, but some are. And never read the comments.
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This is a beautiful pape but it does tempt me to rebrand my non-specific inhibitors as 'location agnostic.'
Location-agnostic site-specific protein bioconjugation via Baylis Hillman adducts
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