Out now in
@CellCellPress
- a perfect way to cap my PhD before convocation tomorrow! [1/5]
POT1 recruits and regulates CST-Polα/primase at human telomeres
So excited to share the preprint from what I’ve been working on in the second part of my PhD! We determined cryo-EM structures of human CST bound to its shelterin recruitment factors POT1 and TPP1. 1/
Incredibly honored to be part of the 2024
@SchmidtFellows
cohort!
Sidenote- officially defended my PhD last week 🥳 Looking forward to pursuing new, exciting questions with interdisciplinary approaches in my postdoctoral studies (location tbd)
Thrilled to share a preprint of my first first-author paper! We determined the cryo-EM structure of a CST-Pola/Primase (CST-PP) complex captured in a recruitment state (1/7)
Now online in
@NatureSMB
!
Thankful for an efficient and constructive peer-review process- it helped us add some very exciting new insights to our story. Short thread on how the preprint (QT) *evolved* (1/6)
Thrilled to share a preprint of my first first-author paper! We determined the cryo-EM structure of a CST-Pola/Primase (CST-PP) complex captured in a recruitment state (1/7)
Incredibly disappointed in
@RockefellerUniv
right now:
(1) admin was completely silent until just now, and the statement is weak at best
(2) the response to the NYC curfew came first, & it wrongly assumes all employees are privileged enough to be safe on the street after hours
Sliced my finger open - PA saw & stitched me up; she was amazing
Dr (old yt man) comes as I’m getting discharged and warns about wearing gloves; I ask him to clarify bc I have to for work
Dr: oh if you work in a restaurant and wash dishes all day then idk what to tell you (1/2)
Monterey Park was where I grew up. It was where my grandparents felt the most at home in the US. They went back to live in China, but they still found their old friends in the same spots when they came to visit over a decade later. My heart hurts.
My two co-advisors both have cats and each periodically send out funny cat videos and cat-related papers to an email thread of the cat people in their labs (and each other), and I get all of them and it makes me very happy
Passed my qualifying/candidacy exam over Zoom and my roommates were so sweet and put up signs and made a cake to celebrate with me at home ❤️
Don’t mind me not noticing the cake with lit candles until almost burning myself...
Finally went back for some CA sun!
Was a highlight to stop by Caltech & see the
@hoelza
lab again for Dr.
@StefanPetrovicc
’s stellar thesis defense (big things coming soon 👀)
Also great to catch up w/ Bil
@clemonslab
- so lucky to have had amazing mentors throughout my career!
Happy Friday to everyone except the yt male grad student who feels the need to publicly question my judgement on what is considered “essential” to my research on a subject very different from his own because he has *1* year of seniority on me in the lab
Although we couldn’t get to high res with FL PP, we see addtl density in our reconstructions, suggesting that the N-term of POLA1 (and we think the globular POLA2 NTD, flexibly attached) bridges to Ctc1 where those other mutations are observed (6/7)
Such an important thread here- John is one of the best scientists (and mentor and friend) I’ve been lucky to know, and this has been a Herculean effort on his part. The resilience needed in science can’t be underestimated- thank you for sharing!
OK so I've got a preprint coming out tomorrow but before it does I thought I'd do a pre-torial to go over the approximately 2.5 years of work on this project that DIDN'T make it into the manuscript to demonstrate the practical aspects of the 'science is hard' theory
Me: ?? I work in a lab across the street and I have to…
Dr: nods, cuts me off, and says “if you’re gardening just make sure you don’t soil the wound”
Me: …
wtf are these assumptions
(2/2)
Huge shoutout to thank
@oliwiagoldman
as well and everyone else here at
@ru_risi
- so proud to work with such an amazing group of people. We will keep fighting!
The last few days have been incredibly rough and I’ve been finding solace in reflecting on shared trauma with AAPI friends and reading words from AAPI writers that capture the grief, anger, and exhaustion we have been collectively feeling.
Really just cancelled all my NYE (and bday!) plans out of caution just to have an unmasked woman on the R cough and spit on the floor multiple times across from me. Threw in a nice “Chinese bitch” when I moved to the other end of the car. Double masked but uncertain again & angry
A new special issue of Science reveals a near-atomic picture of the human
#NuclearPoreComplex
—an elaborate structure composed of hundreds of proteins that mediates the exchange of material between a cell’s nucleus and the surrounding cytoplasm.
Read more:
This mini thread was mainly an excuse to share that last image (we have some other cool findings and speculations in the paper) but super excited to get this out there and eternally grateful to my lab members for their support- esp
@HoorayForZinder
! (7/7)
Hi 👋 I’m Lindsey, a third year PhD student at Rockefeller University studying the neuronal basis of social behavior in ants 🐜
I’m a mixed race 🇨🇻 woman and outside of lab enjoy yoga, playing with my cats, and baking!
#BlackInNeuroRollCall
#BlackInNeuroWeek
#BlackWomenInNeuro
My most shameful secret is copying figures from Illustrator into a blank Keynote slide and then copying from Keynote to PowerPoint because I’m still living in the 2000s and haven’t switched over to using Keynote to make full presentations
Outlook is the absolute worst and now the university is forcing me to use it so apologies to the 6 listservs I emailed today with a messed up attachment 🫠
My favorite
@edyong209
piece so far, and that’s really saying something- the first time I’ve seen the nature of science (and all of its nuances, good and bad) covered so accurately for a general audience
I hope this piece, using the pandemic as a lens, shows how science actually works; how research is funded, done, assessed, and discussed; and how the noble pursuit of knowledge collides with messy reality of an all-too-human endeavour. 8/
Love these articles by
@sarahzhang
Still amazed by the effectiveness of these drugs: for 84 days, we injected one of our cats with ~3 mL of a pH 2 (!) solution from the black market. He’s fully cured now!
Hopefully these life-saving drugs can get approved for cats soon!
“Change is not stochastic. Good change is neither assured nor destined. If we consign ourselves to passivity…we will be swallowed by the darkness of a status quo designed and maintained by those who are content to live in world in which inequity, inequality, and injustice reign”
710 days ago, I successfully defended my PhD dissertation.
695 days ago, I, along with
@Yara_Haridy
, reported our PhD advisor, Robert Reisz, for bullying and harassment.
Today, we are sharing our story.
#FossilFriday
#AcademicTwitter
#paleontology
Final version of the shelterin flexibility story is out (and fully open access) at
@PNASNews
Thanks to the journal staff and reviewers for a constructive and efficient peer review process!
And of course, words cannot express my gratitude for Titia and Tom. It's been a wonderful PhD as a student of the 10th floor of RRB
@RockefellerUniv
[5/5]
The plot keeps thickening! This time, the cryo-EM structure of tetrahymena telomerase-CST-pol-α/primase from
@FeigonLab
. Very cool to see the molecular ssDNA tunnel formed by POLA1 and CTC1 is well conserved!
Thanks to AlphaFold modeling from
@DeepMind
, we can show that the presence of a CRL is correlated with the presence of an expanded CTC1 in metazoans. Together with other data from the preprint, our structure captures the telomeric recruitment of PP in its inactive state (4/6)
“I was the world’s most catastrophic grad student, and while every grad student might think that, I objectively was”
If you, like me, have been glued to
@edyong209
’s pieces during the pandemic (& great science coverage pre-pandemic!), this is a fun read
I did an interview with niche publication "The Atlantic" about pandemic reporting, non-pandemic reporting, the time I got a bird named after me, and She-Ra.
Sometimes self care means doing chores that have been put off for far too long- mental health doing much better with a clean space, repotted plants, and the erased guilt of not having done those things earlier
Tri-I community:
The inaugural lecture of the ACCR DEIJ Lecture Series will be this Monday at 12 pm. We are very excited to kick off this series and hope you can join! Webinar link is accessible from Tri-I networks or VPN on the Rockefeller Calendar of Events.
(2) Our structure informs on Coats plus syndrome mutations associated with CST. The 3 residues mapped have been shown to disrupt PP binding to CST, and V665 resides at the main interaction interface. These 3 residues do not contact PP in the PIC complex (4/7)
Why is this a recruitment state? (1) PP is in an auto-inhibited conformation, where the active site of the DNA polymerase (POLA1, green) is blocked by the POLA2 subunit (yellow), so the enzyme is not yet extended for function, as observed in the PIC structure (3/7)
Timely meme that immediately fixed a really annoying ChimeraX visualization problem that has been bugging me for the last two months- thankful
@HoorayForZinder
is active on Twitter and pointed me in this direction 😅
Heard the world of
#sciencetwitter
is the place to be, so here’s to wiping all the cringeworthy high school tweets and starting fresh five years later 🌱
Witnessed a clearly intoxicated woman going the wrong way down a one way street and hit a delivery driver’s bike-both bike and guy are OK (notice her broken front bumper)
Speeds away after we call 911 and report her plates- hoping she got stopped before she hurts anyone else
Notably, our structure captures an interface that uses the N-terminal OB-folds of CTC1, which aren’t in unicellular eukaryotes (e.g. Tetrahymena, a model in the telomere field). On the other side, POLA1 uses a structurally conserved CTC1-Recognition Loop (CRL) to bind CTC1 (3/6)
What about those 2 muts that don’t contact PP in our complex? The puzzling part of this story is that we only got higher res by deleting the disordered N-term of POLA1 (making PP delta N), which is dispensable for catalysis but interacts with CST (5/7)
Huge thanks goes to Hiro (the hero) and my advisors Titia & Tom. I also want to give a special thanks to
@HoorayForZinder
(the expert on all things shelterin biochem) for optimizing the POT1/TPP1 expression/purification and providing the seeds that started this project. 11/11
My favorite part is Figure 3: Alphafold-multimer (
@DeepMind
) predicted the CTC1-SHLD1 interaction in 1 day, and Zack previously identified this region experimentally using a months-long mutagenesis Y2H screen 🤯
A huge thank you to all of my co-authors: Hiro has been working on the genetics of this complex for over a decade now and his knowledge and expertise here was critical to this story. [3/5]
@JeanneGarb
@S__Baksh
@will_pipets
To provide some context into the RiSI statement, several of RU's Muslim community members privately expressed feelings of erasure from the president’s statement that they were too afraid to bring up in a public manner
It’s been proposed that CST and DNA Polα co-evolved in eukaryotes for telomere maintenance (Neal Lue,
@PatrickForterre
), and we see structural evidence for this continued co-evolution in metazoans! (2/6)
@heidi_moss
Thank you, Heidi!! The lab has been following up on the experiments you did many years ago. It’s so cool to be part of a lab with such a long history 😊
More work to be done on how CST might guide this conformational change of Polα/primase, but so happy that this first part of my PhD work is published! Beyond thankful for all the support of my advisors and co-authors through this process (6/6)
Our most recent work is out now on BioRxiv: coming soon to a journal near you! A wonderful collaboration with Francisca Lottersberger’s lab at
#LinkopingUniversity
. This puzzle was years in the making, but it finally fit together: a 🧵 (1/10)
Teague joined as a new research assistant in the lab last summer and wonderfully purified all of the POT1 mutants we used in the revision. Also new from the preprint is a great collaboration with the Cech lab; it was fun working with Art, a legend in telomere biochemistry. [4/5]
On institutional silence and “meritocracy” in academia, industry, government, and beyond:
“This is racism in the third degree, akin to involuntary manslaughter: We are not trying to hurt anyone, but we create the conditions that shatter somebody else’s future aspirations”
So mad about this for the driver, whose first reaction was to have someone help call the customer saying the delivery was late…
& also bc I and my friends bike to get around & the last thing I want to be worried about is getting hit by a drunk driver. Be safe out there y’all!
By chemically cross-linking CST-PP, we captured a state distinct from the structure of the pre-initiation complex from
@cijilim
, also presented at this week’s
#cshltelo
meeting (2/7)
CST holds (the VERY flexible, as observed by
@HoorayForZinder
) POT1 in a single conformation with three distinct interaction sites. This allowed us to determine the first full-length structure of POT1! 6/
We think our structure of the recruitment state is particularly cool in the context of recent structures from
@cijilim
and
@FeigonLab
showing a conserved mode of binding to extended Polα/primase using the other half of CST! (5/6)
CST–POT1 is a tricky complex. We only got an interaction by engineering a 4 aa insertion (ESDL from mPOT1b) into the hinge of human POT1. This enhances the phosphorylation of human POT1 and we can turn the interaction back off with phosphatase. 7/
@EvanZhao6
Haha we were biking (on very empty streets) and saw someone taking photos, but we assumed they were either a hobbyist or local news- did not expect the photos to be sold to major networks!