Why is there so much disorder in eukaryotic proteins? What is its relationship with condensates? Why can some proteins be saved but others get degraded? After years in the making, we think we have answers and they're all connected. Excited to share a 🧵:
What makes these amino acids different from all the other amino acids?
Together with our collaborators
@KlaraH_lab
, we think we know. The answer is foldability. Protein folding steered the course of the Origin of Life, out now in
@J_A_C_S
.
Very excited to share that our work on Protein Nonrefoldability is out today in
@J_A_C_S
!
#AlphaFold
might be great at finding proteins' native structures... but turns out many proteins themselves are not! Short 🧵1/7
Excited to share, along with brilliant collaborators,
@BookerMan_PSU
& Ed O'Brien
@psu_chemistry
, our paper in
@NatureChemistry
explaining the biophysical basis of how synonymous codon mutations can alter protein structure and function. Short 🧵1/9.
Excited to share our story out in
@NatureComms
in collab. with Ed O'Brien's lab
@psu_chemistry
led by the amazing Dan Nissley
@OxfordStats
. We show that many E.coli proteins can misfold in subtle ways that would bypass the proteostasis network. Short 🧵
When I was a student, I hated troubleshooting. Now as a Jr. PI, that’s what I do: I’m the troubleshooter-in-chief. But now I like it. Why?
1) it’s easier when you have more psychological distance from the failed result.
2) the joy on a student’s face when you help them solve it
We're excited to share new tools, using photo-crosslinking mass spec 💡⚔️⚖️ to study protein structures and complexes in situ with high spatial and temporal resolution. Out now in
@AmerChemSociety
@an_chem
. Short 🧵 1/8
In taking time away from work because I need to (or want to) spend time w/ Liora, I have found a special camaraderie with female colleagues and scientific heroes. Because of the work YOU did over the past generation, we are ALL beneficiaries. Gender Equity is Equity for Everyone
Honoured and proud to be part of the 2024 cohort of
#SloanFellow
s! Would not have been possible without mentors, collaborators, and brave graduate students willing to take on new ideas and try difficult experiments. Thank you
@SloanFoundation
!
@JHUChemistry
@JHU_Mol_Biophys
If you teach a biochemistry class, consider adopting the terminology of Watson-Crick-Franklin base pairing 👩🔬 🧬.
It rolls well off the tongue. Your students will appreciate it. And we can do a small part to right a bad scientific injustice from the previous generation.
#USHUPO2023
was my first
@us_hupo
but certainly will not be my last! We in proteomics are lucky to have such a fun and supportive community. The PI poster session is a great idea: helps lower barriers for trainees to interact with PIs; more conferences should try this!
Hey directed evolution people, our little improvement to error-prone PCR is published in Analytical Biochemistry. Potentially useful to some of you. Great work to
@fried_lab
's Sea On Lee for discovering this. A short 🧵: 1/5
Excited to share that Proteome-wide Photo-crosslinking Mass Spec (💡⚔️-⚖️📊) is now a "thing!" Thanks to
@AphettoChemist
&
@rx_piyoosh
, we can now visualize protein networks and quinary interactions at residue-level resolution in cells. 1/8
#TeamMassSpec
Is it time to relegate the
#RNAWorld
hypothesis in how we think about the
#OriginOfLife
? YES. We share a New Perspective in J.
@royalsociety
emphasizing how peptides and polynucleotides worked TOGETHER to move life forward. A short tweetorial 🧵 1/6
Okay yes, I also got these books along with all the other needy parents. I can assure you they are great fun, and your baby will learn no QM (so don’t have to worry about any spoilers). Can we please get Proteomics For Babies now? 😅
Filling out recommendations for my undergrad applying to grad school... Just want to say: big shout out to
@UChicago
👐for NOT asking those goofy numerical questions that pigeon-hole students. More unis should do this.
@AcademicChatter
#phdlife
Some exciting news from
@fried_lab
undergrads, who have been up to wonderful things!
Update
#1
: Our amazing Ashma Pandya will be headed to
@CalTech
/
@NASAJPL
for grad school as an
@NSF
#GRFP
pre-doctoral fellow, to continue her explorations of astrobiology. 1/4.
#FriedLabNews
Don't think I've announced this yet... but here is my registration to
@GordonConf
#ProteinFolding
#Dynamics
! Life's dynamics are going to get a lot more complicated soon! 😅 (Oh and BTW, registration is open for GRC PFD... check it out, it will be an amazing program!)
1 yr ago, a talented Turkish biochem student emailed me that she was passionate about
#ProteinFolding
... and now İdil Demiralp will be starting grad school at
@scrippsresearch
! So happy
@fried_lab
could be a small part of your scientific journey! Good luck, İdil!
#FriedLabNews
#Folding
can be hard.
Fortunately E. coli proteins
#DontHaveToFoldAlone
.
The cytosolic medium and its chaperones can ~nearly~ fully restore an unfolded E. coli proteome.
In our new preprint, we show how. Short thread 1/8.
To my amazing partner, Daniela: you are my HSP70. When I’m all tangled up, you straighten me out… and then let me slowly become myself again. You are essential to my viability. 🥰😅
#AcademicChatter
#proteinFolding
Big congrats to
@fried_lab
’s Sea On Lee and April Xia who both received
#bps22
travel awards
@BiophysicalSoc
!! Come hear them talk about loopable translation and crosslinking mass spec on the nonrefoldable proteome!
#FriedLabNews
So proud of
@AphettoChemist
for brilliantly defending her PhD this week! Anneliese demonstrated high-res proteome-wide photo-crosslinking is possible, and the field of structural biology is transformed because of her! Mazel tov 🎉 ❤️
#ProudPI
#FriedLabNews
Excited to share our new paper, out in
@J_A_C_S
, a collab. with
@JHUChemistry
Marc Greenberg, driven by the amazing
@_marcojacinto
! We discover that oxidized abasic sites in DNA spread their damage by creating electrophilic PTMs on histone lysines. 1/6
Particularly proud of this report in
@JPhysChem
on how we are lowering the barrier to students' success in physical chemistry. If you teach p-chem, and want to help diversify our discipline and enrich students' experience, please read and join
#LABSIP
!
Everything in science is harder to do than your PI thinks. My old advisor used to say "That will take 1 picosecond to do, right?" 😅
Answer: No. (It takes the molecule 1 picosecond to do it, and me much longer to understand why.)
Really honoured to share our work on non-refoldability with
@bioplymrsinvivo
#BPS2021
. Thank you to everyone there for your thoughtful questions! Really looking forward to Day 2.
Very sad to miss all of you cool
#biophysicists
at
#bps22
this year, esp. today’s amazing
@bioplymrsinvivo
program. Though on the flip side, you don’t get to hang out with Liora- so maybe an even trade? 😜 I’ll catch you next year or perhaps earlier
@GordonConf
!
Really honoured to be selected for this award and to join other incredible biophysicists
@dallandrummond
@LisaMJonesLab1
. Thank you so much to the academy! 🤣 🎉 And to
@fried_lab
for all your creativity and hard work to make this possible!
Congrats to
@fried_lab
's Sea On Lee for successfully defending her dissertation AND for being awarded a Gompf Family Fellowship from
@JHUChemistry
! You really impressed your committee and set a high bar for all future grads from the group! 🎉😁
#FriedLabNews
Feeling very happy today 😁; two stories that had long (and at times bumpy) roads both got accepted! Will share tweetorials in due course... for now, just want to thank the peer reviewers out there who (1) are willing to listen to new ideas; (2) want to make papers BETTER. 🙏
Coming back home to Baltimore from Wilmington, DE. What an incredible opportunity to hear
#JoeBiden
and
#KamalaHarrisVP
address our divided nation with hope and humility.
#Election2020
“Now is a time to heal.”
And one belated
#FriedLabNews
— major congrats to Sea On Lee for being our very first Doctor to graduate from the lab!
@JHUArtsSciences
hooding ceremony was beautifully done. Was my 2nd time ever wearing
@Stanford
’s gown (hard to hide in it!) To many more!
Big mazel tov to
@fried_lab
's Divya Yadav for getting an ACS travel reward to attend
#ACSSpring2023
in Indy! Divya has done a proteome-wide assessment of cotranslational protein folding and will be sharing it for the first time!
#FriedLabNews
@JHUChemistry
Blast from the past!
@DrJ_RNA
and I first met in
@lindaunobel
2013. At the time we said- would be cool to postdoc abroad and then come back. Decade later - seeing her at
#bps2023
made my day
Congratulations Steve Boxer
@stanford
on receiving the
@BiophysicalSoc
’s founders award! Very happy we had a chance to reconnect lab alumni and friends from several generations!
#BPS2024
So excited to be co-organizing the 2024 Symposium for
#StructuralProteomics
with
@FJ_OReilly
&
@Malvina_Pap
at
@broadinstitute
in October! Save the date (28-30 Oct) for this event bringing together leaders in structural mass spec, cryoET, comp. structure prediction, and more!
I am so excited by the mission of this
@RCSA1
program and grateful for the opportunity to be part of the
#CotttellScholar
cohort. There is a lot of work to do to improve equity and learning outcomes in STEM! Looking forward to meeting the other scholars.
RCSA has named a diverse group of 24 early career teacher-scholars in chemistry, physics and astronomy as recipients of its 2022
#CottrellScholar
Awards. Each awardee receives $100,000.
Exited to share with y'all that
@ManriquezEdgar
's program for accurately assigning domain architectures, DomainMapper, is now published! Code is on github. Pretty easy to install use. Hope that you find it useful, and happy to get feedback.
.
#ProudPI
moment! Haley Tarbox explains to
@us_hupo
her data showing a general connection between cognitive decline and protein misfolding. Come find her to get your LiP-MS questions answered!
@impetusgrants
@NIGMS
The secret is disorder. The more disorder a protein has the better it refolds (like a built-in chaperone). Yeast proteins have higher levels of disorder than E. coli's, and this neatly explains why they refold better. Same goes for N. crassa, another fungus. 4/10
@fried_lab
's paper on "loopable traslation" is out in
@ACSCentSci
! We designed a system that
#circularizes
#RNA
& is efficiently translated, enabling facile synthesis of repetitive high-MW proteins - potentially useful for making new protein materials.
Great time had by all at Gibbs36!
@rx_piyoosh
's first conference in USA, Haley Moran gave a great talk on Tuesday,
@ManriquezEdgar
shared news with friends about his Prot.Sci. paper getting accepted. Looking forward to next year's!
#FriedLabNews
What an amazing two days at
@WashUChem
and
@WUSM_BMB
, where I had the pleasure to be hosted by friends
@jenheemstra
and
@alexholehouse
and meet many other amazing scientists doing trailblazing biophysics. Thank you for a lovely visit!
Can we teach bacteria to autonomously synthesize and assemble biomaterials?
@Qi_Xieqi
and coworkers thing so! Excited to share our work on secretion-catalyzed assembly, out now in
@angew_chem
. Bacillus's translocon can act like a nano silk spinneret!
Many of you have asked; now we are beginning to work on it! Xinzhe gives his 1st group meeting to
@fried_lab
on methods to probe phospho and glyco on protein folding. Thanks to
@us_hupo
colleagues
@riley_nm1
@GarciaLabMS
who inspired us to take on this new direction.
#glycotime
First lab social since Christmastime 2019!! Thank you 🙏 all for your culinary 🍲 skills and for vaccines 🧬💉that make it possible! Grateful for the chance just to all be together and chat. What’s next??— camping trip?
#FriedLabNews
These awesome authors just submitted their manuscript, and took my suggestion to take the afternoon off! Look out for a tweet on the pre-print soon!
#FriedLabNews
For proteins that can refold spontaneously (like most engineered FPs), folding may not be so sensistive to translation speed. I would be very careful about extrapolating this result to complex proteins whose folding is affected by translation schedule.
See our latest work on the influence of codons on gene expression. Full codon-randomization of a gene in E. coli shows only the first 8 codons really matter! Freely adapting Bill Clinton slogan: It's the first few codons, stupid!
Who on
#TeamMassSpec
loves
#FragPipe
? Edgar has built some beautiful software enabling LiP-MS data to be analyzed at greater depth and with greater sensitivity. We call it FLiPPR, for FragPipe LiP Processor. 1/3
First in-person
@fried_lab
group meeting in... two years😅! (slightly embarrassed to admit -better late than never tho, right?) Thank you
@DivyaYa09490300
for kicking it off with some exciting updates on your new project!
#FriedLabNews
Really excited to kick off
#FiGURE
(first-gen undergrad research experience) today! Six
@JohnsHopkins
freshmen will be exploring protein folding throughout the Tree of Life, and joined their first group meeting today. Looking forward to see what you discover!
#FriedLabNews
We're lucky to have some awesome summer students in
@fried_lab
! Joy Brewer is refolding Bacillus proteomes whilst Mark Fakler and İdil Demiralp are figuring out how protein structures get perturbed when chaperones are missing. Excited to learn what y'all discover.
#FriedLabNews
Statements to this effect seem to have become fashionable lately. "Science is on the decline." "Progress is slowing down."
@ezraklein
interviewed Pat Collison on so-called "Progress Studies" to the same effect. These thinkers are missing something very basic and are very wrong
'Disruptive' science has plummeted — and no one knows why.
Research in the 2000s is much more likely to incrementally push science forward than to veer off in a new direction.
Check out my latest for
@Nature
with
@russellfunk
,
@dashunwang
,
@yian_yin
Our new group photo and first time we’ve all been in the same wide-angle lens frame. Big kudos to Qi Xie for this capturing this brilliant shot even with social distance!
#FriedLabNews
Happy
#YearOfTheOx
to our students of Asian heritage! You contribute so much to the scientific community of
@JHUChemistry
(and across the US)! This year, may you stay 💪as an 🐂 when experiments go wrong; sometimes a little stubbornness and bullheadedness can go a long way 😁
An important read for anyone interested in enzyme mechanism from my PhD mentor (twitterless Steve Boxer
@StanfordChemis1
) and the talented Zhe Ji! The electric field catalysis model explains evolution of beta lactamases.
Do you want to continue hanging out with cool
#biophysicists
after your post-doc? Biophysics
@JohnsHopkins
is hiring! We are trying's
@YaleMBB
method to try to lower bias & diversify the applicant pool. Consider applying! Please RT.
@BlackInBiophys
So excited that this is out in
@NatureSMB
! Firstly, a HUGE shout-out and thanks to the amazing
@valendraica
,
@S4yanDas
, Greg Bowman, and Ilana Nodelman for their
#CryoEM
wizardry 🪄. So what can you learn about nucleosome remodeling at 2.3 Å? It turns out, QUITE A LOT. 1/5
Very excited that our paper is finally out in
@NatureSMB
! Working together with Ilana Nodelman, Greg Bowman,
@fried_lab
,
@AphettoChemist
and
@s4yandas
, we were able to solve the nucleosome-bound yChd1 at 2.3Å 1/2
First time in the office since March 17. Was starting to miss this place! Thanks to
@JHUArtsSciences
for permission to commence a
#COVID19
project. Working with Matthias Heyden & Carlos Simmerling to stop SARS-CoV-2 by throwing a wrench in its
#ribosome
#frameshifting
Big shout-out to
@fried_lab
‘s
@PtoChem
, April Xia, and Atharva Bhagwat for venturing to
#PS36
@ProteinSociety
! If you’re there, go meet with these awesome rising young scientists to learn what biophysical properties help proteins refold!
We’re 3 for 3! All of the 2nd years have passed their GBO exams and are ready to dig more into their projects! Congrats Haley, April,
@ManriquezEdgar
!
#FriedLabNews
Sad that it’s the last day of FiGURE (first-gen undergrad research exp)! Was such a pleasure to teach brilliant
@JohnsHopkins
freshmen about
#LabLife
&
#ProteinFolding
! Excited to see what we discover in your data.
@NSF
-funded
#MCB
.
Just submitted our first manuscript to
@PRX_Life
! -actually first time ever to an
@APSphysics
journal. Looking forward to connecting more with the community of physical biologists that this journal is coalescing together. (Wish us luck with our reviewers! 😅)
We unfolded yeast's proteome and challenged it to refold spontaneously. The result? 🥁... Yeast proteins are surprisingly efficient refolders, much BETTER than E. coli's, despite being larger, having more domains, & more β content. How can this be? 3/10
We made it!
@fried_lab
has trekked to Carbondale for the 37th annual Nerds in the Woods (AKA,
#Gibbs
#Biothermodynamics
conference). Looking forward to digging into some exciting science from old friends and new acquaintances!
#FriedLabNews
I seldom tweet political but I am so proud of Kansans for voting down an amendment that would have removed constitutional protections for the right to have an abortion in a decisive 60-40 split.
More
#FriedLabNews
: Big congrats to
@fried_lab
students Edgar Manriquez and Yilin Shen for getting travel awards to give talks at
@ABRCMS
! They're going to talk about some new improvements to the
@Quantum_Si
protein sequencing technology and
#chaperones
@fried_lab
shows up for
#BPS2024
! I remember how special it was when as a grad student the whole lab traveled together to the
@BiophysicalSoc
meeting when it was close. So happy I have the chance to carry on that tradition!
#FriedLabNews