Jack Zhang Lab
@zhang_lab
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Jack (Kai) Zhang Lab at Yale University Intracellular Transport, Cell Motility, Mitochondria, Cryo-EM/ET Methodology -- Cellular Structures, Life & Health
New Haven, CT, US
Joined May 2020
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High-res In-situ Structures of Mammalian Respiratory Supercomplexes in Reaction within Native Mitochondria
Check out my lab's first work on membrane proteins!
Yes, we knew nothing about detergent😜, so we directly imaged proteins within native membrane!
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Excited that our lab's first major work is officially published in NSMB! It may just be a minor progress, compared to explosive science and technology advances, but sufficiently important for the field. Thanks to my postdocs and student in this exceedingly challening pandemic
@zhang_lab
@qinhuirao
@Yale
report impressive
#cryoEM
structures of the HUGE outer arm
#dynein
(OAD) assembly on the axoneme that drives rhythmic ciliary beating.
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Since the outset of my career, I’ve always been fascinated by two types of dream research: (1) the intricate and dynamic biological systems, like the cellular transport machinery, and (2) the powerful imaging technologies that allow for visualization of the subtlest motions of
So thrilled to share our lab's most exciting findings, ever, on dynein in collaboration with Steven Markus lab
@lab_markus
!!! Years of hard work on the most challenging and mysterious cellular vehicle now rewarded: Dynein-1, a fascinating motor protein & the most dynamic molecule
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After years of struggle in vain, the Zhang lab would like to express our deepest gratitude to THE six nicest reviewers of the world, including 3 for our lab's first paper on outer-arm dynein arrays bound to microtubule doublets, and the other 3 for our first NIH R35. (1/3)
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Cryo-EM structures of outer-arm dynein array bound to microtubule doublet reveal a mechanism for motor coordination
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How does dynein cycle its conformations and takes one step forward along the MT?
Check out our exciting new results unveiling the atomic details of the conformational space of Reactive Full-length Human Dynein-1, on and off microtubules:
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We are pleased to share our structure with the community. PDBs also available!
A stunning & comprehensive structural tour of the active cilia central apparatus by
@zhang_lab
- not only shows organisation of projection & bridge proteins but also captures arrays of kinesins (in different stepping states!)
#journalclub
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Dear Cilia Friends,
To maximize the benefits of the field, particularly for those who need PDBs for ciliopathies-related mutagenesis, my lab is very pleased to announce we have a huge atomic model of nearly entire central apparatus in hand for over a year.
Feel free to contact
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So thrilled to share our lab's most exciting findings, ever, on dynein in collaboration with Steven Markus lab
@lab_markus
!!! Years of hard work on the most challenging and mysterious cellular vehicle now rewarded: Dynein-1, a fascinating motor protein & the most dynamic molecule
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Our team seems so 'tiny', compared to the many huge labs like gigantic army groups, yet each member is indispensable to the success of this level of work! I am immensely proud of my postdoc Wan, student Pengxin & long-term collaborator Prof. Zhu for their enormous contributions!
High-res In-situ Structures of Mammalian Respiratory Supercomplexes in Reaction within Native Mitochondria
Check out my lab's first work on membrane proteins!
Yes, we knew nothing about detergent😜, so we directly imaged proteins within native membrane!
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Dynein is dynamic, dynein is 'naughty', dynein is everywhere in cells, but too hard to capture their conformations due to the extreme flexibility. By leveraging the real power of cryo-EM for dynamic structural analysis, we reveal a whole series of intermediates states of
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Congratulations, Ziao! Super cool! Bending the membranes bound at both ends. Structure of the Flotillin Complex in a Native Membrane Environment
See also our respirasome structures in the native membrane:
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Behind this incredible honor is Andrew's more than 20 years of tireless, dedicated work to master the most dynamic, flexible, and mysterious molecule that defines the true meaning of life's movement within cells.
This is not just an honor but also a deeply encouraging
Congratulations to Andrew Carter (
@Carter_lab
), Group Leader in the LMB’s Structural Studies Division, who is elected Fellow of the
@royalsociety
.
Read more here:
#LMBNews
#royalsociety
(1/2)
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A 5-day intensive, concentrated cryo-EM workshop at Yale has been going very well! Pengxin, my stellar student at the podium, is delivering incredible tutorials on cryo-EM data processing (nearly all aspects). Yesterday, Relion & today, cryoSPARC.
#CryoEMWorkshop
#Yale
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Congratulations to Andrew!
Behind the glory, it is 20 years of persevering hard work to harness one of the most challenging and mysterious molecular machines that drives cellular cargo movement.
Congratulations to Andrew Carter (
@Carter_Lab
), Group Leader in the LMB’s Structural Studies Division, who is the 2023 recipient of the Hooke Medal from
@Official_BSCB
!
Read more about Andrew and his research on cytoplasmic dynein here:
#LMBNews
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So excited to share our latest progress in collaboration with the Markus lab at the critical intersection of three major directions regarding dynein's functions, structures and regulations: (1) MT-binding, (2) Lis1 interaction and its regulatory roles, and (3) nucleotide cycle.
Excited to share a new preprint from the lab about dynein and LIS1! Very productive collaboration with the cryoEM wizards,
@zhang_lab
,
@YueWang61171374
,
@PengxinC
. We show how dynein-LIS1 binding/unbinding is regulated by dynein conformation.
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Thank you very much, Pleasantine! I did't realize you had already annouced it one month earlier😂 than the official meeting date. We are more than honored to receive this great award in memory of Prof. Gibbons and take the opportunity to present!
...
@qinhuirao
&
#newPI
@zhang_lab
for Stunning cryo-EM of full OAD complexes bound to
#microtubules
. Also mechanism for inter-dynein coordination to produce movement within
#cilia
. They get the Gibbons Award lecture at
#Dynein2021
& cash prize. 👏👏👏 /2
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Despite the many 'insane' obstacles (believe it or not), I must highlight the infinite support from my exceptionally inspiring colleagues and those real scientists who truly understand the potential impacts of this work, including Yong, Joe, Anna, Fred, Jun & more!
High-res In-situ Structures of Mammalian Respiratory Supercomplexes in Reaction within Native Mitochondria
Check out my lab's first work on membrane proteins!
Yes, we knew nothing about detergent😜, so we directly imaged proteins within native membrane!
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Alexey's video, by putting these static figures together in a more visible way, has made our work more impressive! Thank you so much!
@A_Amunts
Amazing mitochondria in situ by Kai
@zhang_lab
! Respiratory supercomplexes in their native states up to 1.8-Å resolution. Four different supercomplex organizations impact the local geometry of the membranes, and reactive intermediates of CI and CIII are captured too.
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Still remember one of my first questions 7 years ago when I started in Andrew's lab: why don't we directly work on dynein-MT?
It wasn't until 2019 that my lab could start taking a glimpse of a <30A map and I realized how silly a question I had asked then.
A closer look at these beautiful structures for
#journalclub
, which provide a better understanding of how motors coordinate during ciliary beating.
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Honestly, I'm OK with eternal rejections. I do research for fun, not for funds, but these nicest 6 reviewers indeed saved my postdocs' lives, or they have to leave and look for new jobs (the one who built the entire central apparatus model already left for insufficient funds) 3/3
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A very Merry Christmas & 圣诞快乐 & 聖誕快樂 to LMB old friends and colleagues! Hope everyone is doing well and enjoy the holidays.
So sad to know that 汉语/漢語 is the most difficult language to learn in the whole world!
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I really enjoyed talking with some senior scientists who have eternally young minds, appreciate everything from young scientists and constantly get excited by new findings from the new generation. This is the real way how the whole field could maximumly benefit from each other.
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I had no idea about the impact score at the begining and was so nervous when I saw it was 10, but was very surprised to find out that it actually means the highest possible score, even though we knew it's not worth that high. (2/3)
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The Zhang lab is warmly welcoming two excellent female scientists ~~~ So happy and grateful that they decided to join us!
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Very glad to see this collaborative work with Steven's excellent team is officially out!
Excited to see the final version of our story about dynein and LIS1! Fun collaboration with
@zhang_lab
,
@PengxinC
,
@YueWang61171374
!
This version has additional biochemical data and structural analysis than our prior
@biorxivpreprint
.
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A dynein-associated photoreceptor protein prevents ciliary acclimation to blue light
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Honestly, we don't care about where a real breakthrough work is published. Many old papers on JMB/JBC/JSB without any colorful figures look much much much much much better (sorry, not a native speaker) than many flamboyant modern papers on luxurious top fashion journals.
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Just had a really great visit to
@StJudeResearch
Memphis, seeing quite a few old friends/colleagues and making new friends. It is a fantastic place, great scientists, great support, so many exciting/surprising research works moving on...Thank you
@JiSunLab
so much for the invite!
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Thanks, Pleasantine! The e-symposium is really great. Particularly, we like Girish and Rui's questions very much.
Another amazing talk in wave of
#preprints
of stunning structures & mechanisms of how axonemal
#dyneins
are arranged on
#MTDs
in order to drive a coordinated beat-
@QunhuiRao
from
@zhang_lab
@YaleMed
ICYMI:
#ukcilia2021
3/7
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Many may not know: 15 years ago, I myself actually started my own PhD work by imaging mitochondria using cryo-ET. It was almost nightmare experience. No surprise, that part of work did not generate any publishable results, as I was feeling like imaging blobs all the time!
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Congratulations!
Congratulations to Andrew Carter (
@Carter_lab
), Group Leader in the LMB’s Structural Studies Division, who is elected Fellow of the
@royalsociety
.
Read more here:
#LMBNews
#royalsociety
(1/2)
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15 years later, it was such a pleasant experience working together with Wan and Prof. Zhu, as well as my student Pengxin to unveil the incredibly stunning beauty of mitochondrial proteins at this level of high resolution within the native membrane environment!
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Very nice work from McKenney and Markus labs
Conserved Roles for the Dynein Intermediate Chain and Ndel1 in Assembly and Activation of Dynein
#bioRxiv
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The authors report a cryo-EM structure of Mars in unprecedented details, which is truly impressive itself. However, the interest is only limited to the field and the implication in possible human immigration is whimsical. Thefore, we suggest publication in a specialized journal.
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Exciting kenesin motors bound to microtubules
We believe every motor structure in the MT-bound state is extremely important and insightful for us to really understand the ultimate meaning of Life.
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MINFLUX Reveals Dynein Stepping in Live Neurons
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@bengeliscious
@HugovandenHoek
@nikolai_klena
@MareikeJordan
@3P1L
@williamnwan
@GaiaPigino
@CentrioleLab
@PioneerCampus
@humantechnopole
@UNIGEnews
Just wow! Needless to say, this is the most beautiful work that demostrates the real power of structural biology and its real future, and something that could never be replaced by Alpha-fold, at least not within our life time (kill me if Yes).
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@KenichiTsuda4
Exactly! 千人計画 is just a research award program open for WHOMEVER NOT from an institution in the mainland China, nothing else, but the western media and politicians tend to exaggerate its political impacts. That is really misleading.
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@CentrioleLab
Thank you so much for sharing our preprint!
Actually, we had already got a ‘very good’ structure in hand in 2019, but it shockingly took us more than two years to ‘finalize’ this giant… Never in my life would I like to carry out such a project again...
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So proud to have such highly impressive, very hard-working, productive and talented collaborators & my postdoc Yue and student Pengxin. My deepest gratitude to all people in both labs on this. Just check it out. So much information. Lots of interesting findings ...
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Years ago, (1) I copied my codes to a 'collaborator'. Months later, they submitted a paper without mentioning me and my work at all.
(2) I provided the key idea for another work with 'proof-of-concept' test; an arrogant boss on the paper tried to despise me: 'idea is cheap'.
A small number of people know the real background story to
@QuPath
, but most don't.
I didn't plan to ever tell it publicly, until a Google Alert today caught my eye.
A thread about open science & academia 👇 (1/n)
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UExM unveils the mystery of centriole assembly!
Thanks to this systematic analysis using
#UExM
, we were able to propose a model of centriole assembly made by
@RibosomeStudio
and
@MargotRiggi
which starts with a naked cartwheel, a bloom phase, and the assembly of the other structural elements.
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Very impressive movie showing how the dynein-driven intercellular transport machinery is assembled! Yet, this might be just the start to understand the very complex assembly mechanism, and many intriguing mysteries still remain to addressed.
Check out this stunning animation by
@janetiwasa
(in collaboration with
@SamReckPeterson
), showcasing our model of how various components come together to form active dynein complexes capable of transporting cellular cargo.
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Side note (1): the paper was published in a very small journal in Chinese not even known by most Chinese scholars and her contribution had not been recognized for nearly 40 years until ~10 years ago!
Tu Youyou discovered artemisinin – an anti-malarial that has saved the lives of millions of people worldwide.
Tu not only found a way to extract artemisinin from a traditional Chinese medicine, she also tested the new drug on herself to speed up development.
#WomenInScience
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How does an infectious bacterium move in host cells? New finding reveals that the autotransporter protein ScaC recruits the dynein adaptor BICD2 to bacterial surface.
Excited to share our new study on an unusual dynein cargo: an intracellular bacterium! We show that Orientia tsutsugamushi hijacks dynein via BICD2 adaptors. Led by
@GiuliaManigras1
with
@JSalje
's group. Out now in
@biorxivpreprint
! A thread 🧵 (1/6)
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@GaiaPigino
@CarstenJanke
@Sudiya14
@gonch_o
This is really beautiful!!! Congratulations!
I hope such a wonderful work will also contribute to drawing people's attention to general mechanisms of the cilium system, which is very important but still severely undervalued compared to other 'hot' fields in the past!
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@Zephyris
Yes, my postdoc overcame numerous technical barriers. He did very brilliant tricks in sample preps, collected many different types of data, developped a whole bunch of comprehensive data processing appraoches, and revealed an absolutely stunning role in beating regulation.
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@RuiZhangWUSTL
@sami_chaaban
@GaryBrouhard
If I were Jack Ma (instead of Jack Zhang), I would give you 10 times more money than you need to carry it out😀🙌👍
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@Mill_lab
@qinhuirao
Thank you so much for your appreciation, Pleasantine! Time flies. The COVID-19 makes new labs older much more quickly than ever before. Submitting 'cilia' papers to top journals turns young PIs old instantly😂 Hopefully, we can still be alive and be 'brained' without a cilium💪
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@bengeliscious
@IsraelF96135088
Plus a three-year-old constantly saying "play with me" at any possible time ...😂😅
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Science Has No National Borders
In honor of Asian/Pacific American Heritage Month, we are celebrating the important work and accomplishments of Asian and Pacific Islander scientists. Follow along on this thread for the rest of May for highlights!
#APAHM2021
#AAPI
#APAHM
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@Riottowow
Ten years ago, when I was a student, an old professor told me, "in your early career, you have to work ten times harder and get ten times better results than an authoritative professor does to earn ten percent credit of his if you happen to work on a similar project".
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I forgot to mention there are many supportive scientists outside the field. They truly appreciates the importance, impacts & unlimited potentials of future cryo-EM/ET, including THE (yes, THE) former MB&B chair, Prof. Hochstrasser who recruited & fully supports the Zhang lab.
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Thanks, Pleasantine! Thanks for organizing such an amazing series of meetings on cilia. All people in my lab highly appreciate it!
Great global
#cilia
&
#centrosome
science, we have lined-up for you
@Jayslab2
, the Dammerman lab, the
@zhang_lab
,
@yusifov_elxan
(Stoeckli lab), new PIs from the Kulkarni and Hilgendorf labs! Don't miss it!
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When you launch a projectile, it strictly follows a parabola path and never violates the physical laws. However, if you do the same thing to a bird, it flies away. That level of movement is the real meaning of Life and it is driven by many molecular motors bound to cytoskeletons.
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@PascalAlbanese
My postdoc Wan was trained to become an artist when she was a child. She did not like that, decided to purse a different career, and then obtained a medical degree. Now she's working on structural biology. It is Wan's idea to illustrate this dynamic process in such a vivid way😂
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@MiWieczor
Thank you so much! Indeed, think about the fact: how flexible it is, how many conformations coexist!!! Seeing water molecules in a complex like dynein is already stunning enough itself, yet, this only counts for 1% of Pengxin and my postdocs' work in this paper!
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Cannot agree more!
Is publication in a high impact-factor journal essential for a Nobel Prize?
Read more about what Martin Chalfie and other Nobel Laureates have to say about journal impact factors:
#NobelPrize
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My colleague is looking for a postdoc. Great opportunity for cryo-EM methods!
We’re hiring postdocs in
#cryoEM
#algorithms
at
#Yale
! Join us to take a fresh look at algorithms for cryo-electron microscopy: heterogeneity, inference, and models (mathematics of data science position also available)
#postdoc
#positions
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Side note (2): The work itself had been recognized much earlier and was indeed awarded for multiple times, both in China and internationally, but Tu was never among those awardees. Instead, it was Tu's leading officials who got awarded.
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As a scientist, will you do something that you believe is very important but will probably not be funded in a short while?
Yes
35
No
2
Yes, but practically No
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@A_Amunts
Oh, NO!!! I did not realize that at all! So shocked and so sorry to hear this very sad news!😭 We substantially revised the discussion based on Prof. Wikström's invaluable suggestion.
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@StearnsLab
Thank you so much for your appreciation! Hope our structure of this huge machine could help raise more interesting questions and potentially initiate new studies on motile cilia.😀
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@jbwallingford
Thank you, John! Hope our structure will more or less help your work. The central pair kinesin is sooo amazing...
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@Hanting_Yang
Thanks, Hanting! Hope everything is going well with you and your lab setup at Fudan University. Wish you a successful start!
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@DrDidychuk
@YaleMBB
@DamonRunyon
@C_P_Lapointe
@dianyang1117
@xzhang85
@xinzhoulab
Congratulations, Allison! We can't wait to see you at Yale!
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In situ structure of the AcrAB-TolC efflux pump at subnanometer resolution
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@NavinPokala
Actually, not just the hole in the nitrogenous base, but also that in the ribose in the best map😀
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We are now able to advance 'one more step toward this ultimate goal,' much like dyneins progressing a tiny but steady step forward along microtubules, together with my student Pengxin Chai
@PengxinC
, my postdocs Yue Wang
@YueWang61171374
and Jun Yang, as well as my long-term
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@BolandLab_GE
Many thanks, Andi! Since 10 ten years ago we knew each other in MRC-LMB, your work has always been highly impressive, each time, every paper! :)
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Well done, Oliver!👍
Happy to share our new
@biorxivpreprint
: “Architecture of the human erythrocyte ankyrin-1 complex” from Clarke lab (first author the incredibly talented
@Frances84469032
) and collaborators
@lab_cali
and
@alexjamesnoble
! Read on to find out more (it was a surprise package…):
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@ZihniLab
@Carter_Lab
Thank you so much! It is always the real experts that appreciate deep studies. Mutual appreciation :)
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@bengeliscious
@IsraelF96135088
Haha, that is a good question! Things are sometimes much harder than expected, not just about research, especially when the PI wants something more sustainable for long-term goals, but the lab needs papers/funds to survive and postdocs need 'fancy papers' within reasonable time.
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Academic dignity: Leave the bookcase there, perish on it.
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@NS_Malvankar
Thanks, Nikhil! Compared to your nanowire work, which is much much more fancy and attractive, our research sounds too 'basic' :)
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@GirishRMali
Thanks, Girish! It was expected that this level of structural work would 'seed' many more questions (opportunities) than the structure itself could address. Hope our structure will improve the situation that we could not even have a chance to begin asking deeper questions.
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@NS_Malvankar
@BuddySphinx
@Aldo_Salazar13
@SibelEbruYalcin
@YaleMBB
@YaleWestCampus
Congratulations, Nikhil! We done on such a beautiful story! Awesome work!
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@MatteoAll
Thank you so much, Matteo! I have always been deeply impressed by your work as well!
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Based on decades of hard work and so many brilliant ideas from those outstanding scientists contributing to the dynein field, combined with our own exciting results by dynamic cryo-EM analysis, we now propose a substantially revised model of dynein mechanochemical cycle:
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