Tina Perica
@glukozica.bsky.social
Assistant professor of Biochemistry, University of Zurich
Lab: https://perica.bioc.uzh.ch
Too school for cool
Lab: https://perica.bioc.uzh.ch
Too school for cool
Reposted by Tina Perica
New paper “Proteome-wide model for human disease genetics” is now live at Nature Genetics: rdcu.be/eRu7K
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
November 24, 2025 at 2:53 PM
New paper “Proteome-wide model for human disease genetics” is now live at Nature Genetics: rdcu.be/eRu7K
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:
This is bound to be a great place!
Could you be our new professor in protein design? Join the Novo Nordisk Foundation Center for Protein Design (cpd.ku.dk) in beautiful Copenhagen. Superb new facilities, smart students and great colleagues. Apply:
jobportal.ku.dk/videnskabeli...
jobportal.ku.dk/videnskabeli...
Center for Protein Design – University of Copenhagen
To accelerate protein design by developing a deeper understanding of sequence-to-structure/function relationships in proteins, and methods to programme these into functional designed proteins
cpd.ku.dk
November 24, 2025 at 7:05 AM
This is bound to be a great place!
This.
Scientific journals: we don’t want you using generative AI because it makes shit up.
Same journal: here is an AI summary or evaluation of this paper. This might be more useful than the actual abstract or paper that the authors freaking wrote
Same journal: AI cover art which makes no sense? Oooh!
Same journal: here is an AI summary or evaluation of this paper. This might be more useful than the actual abstract or paper that the authors freaking wrote
Same journal: AI cover art which makes no sense? Oooh!
November 23, 2025 at 10:54 AM
This.
Reading that text I was convinced that this lady is indeed no intellect, just emotions. No facts or math, just gossip. And then she just concluded all women must be like that.
November 6, 2025 at 5:49 PM
Reading that text I was convinced that this lady is indeed no intellect, just emotions. No facts or math, just gossip. And then she just concluded all women must be like that.
May her memory be a blessing.
Zara Weinberg passed away earlier this week. She joined my lab earlier this year when her postdoc lab formally closed.
She was a brilliant scientist, supportive mentor, dear friend, avid music fan, rabid believer in public transit, open science champion, and above all just an amazing human.
She was a brilliant scientist, supportive mentor, dear friend, avid music fan, rabid believer in public transit, open science champion, and above all just an amazing human.
November 1, 2025 at 9:22 AM
May her memory be a blessing.
Reposted by Tina Perica
The amount of AI generated art in slides at this conference, primarily used by older scientists, is killing me. Scientists please. Don’t use these ai platforms to make your figures or slides. They look bad and I have yet to see them meaningfully improve the message of talks.
October 31, 2025 at 3:09 AM
The amount of AI generated art in slides at this conference, primarily used by older scientists, is killing me. Scientists please. Don’t use these ai platforms to make your figures or slides. They look bad and I have yet to see them meaningfully improve the message of talks.
Oh, bloody brilliant! Guess what I’m replying next time I don’t care to review something!
Nothing can prepare you for the factual basis behind this 'wokeness gone too far' anecdote.
October 28, 2025 at 3:26 PM
Oh, bloody brilliant! Guess what I’m replying next time I don’t care to review something!
Nice work. Thanks for a fantastic skeetorial, always appreciated
October 22, 2025 at 7:09 PM
Nice work. Thanks for a fantastic skeetorial, always appreciated
Reposted by Tina Perica
The @nytimes.com decided last year what the story was; Trump II was the righteous punishment visited upon their interns and junior staffers and grandchildren for being so annoying about MeToo and BLM, and once they understood that and repented, they could have democracy back.
October 21, 2025 at 1:57 AM
The @nytimes.com decided last year what the story was; Trump II was the righteous punishment visited upon their interns and junior staffers and grandchildren for being so annoying about MeToo and BLM, and once they understood that and repented, they could have democracy back.
Reposted by Tina Perica
I wrote a blog post about the future of structural bioinformatics.
Where to go after AlphaFold? How do we avoid the field becoming a load of half-baked LLMs?
Let me know what you think.
jgreener64.github.io/posts/struct...
Where to go after AlphaFold? How do we avoid the field becoming a load of half-baked LLMs?
Let me know what you think.
jgreener64.github.io/posts/struct...
Where next for structural bioinformatics?
jgreener64.github.io
October 15, 2025 at 2:16 PM
I wrote a blog post about the future of structural bioinformatics.
Where to go after AlphaFold? How do we avoid the field becoming a load of half-baked LLMs?
Let me know what you think.
jgreener64.github.io/posts/struct...
Where to go after AlphaFold? How do we avoid the field becoming a load of half-baked LLMs?
Let me know what you think.
jgreener64.github.io/posts/struct...
I’ll let you know if we see anything interesting!
October 14, 2025 at 2:10 PM
I’ll let you know if we see anything interesting!
One thing is for sure, fun with RAF never ends! (10/10)
October 14, 2025 at 8:17 AM
One thing is for sure, fun with RAF never ends! (10/10)
One thing took us by surprise: It seems that the asymmetric dimer comes at the end of the RAF activation cycle. We got more structures and saw that the Receiver looks the most like a canonical active kinase. Is the asymmetric conformation then the final catalytically active state of RAF? (9/10)
October 14, 2025 at 8:17 AM
One thing took us by surprise: It seems that the asymmetric dimer comes at the end of the RAF activation cycle. We got more structures and saw that the Receiver looks the most like a canonical active kinase. Is the asymmetric conformation then the final catalytically active state of RAF? (9/10)
If we titrate those mutants into cells with wild type RAFs in the background, we should see a dose dependent effect. And we did. The beautiful model must be correct! (8/10)
October 14, 2025 at 8:17 AM
If we titrate those mutants into cells with wild type RAFs in the background, we should see a dose dependent effect. And we did. The beautiful model must be correct! (8/10)
But what is the difference between active asymmetric and active symmetric structures? We made BRAF mutants
(i) AAAA mutant = Receiver but not Activator
(ii) Kinase-dead mutant = Activator but not Receiver
(iii) Double mutant = neither
(7/10)
(i) AAAA mutant = Receiver but not Activator
(ii) Kinase-dead mutant = Activator but not Receiver
(iii) Double mutant = neither
(7/10)
October 14, 2025 at 8:17 AM
But what is the difference between active asymmetric and active symmetric structures? We made BRAF mutants
(i) AAAA mutant = Receiver but not Activator
(ii) Kinase-dead mutant = Activator but not Receiver
(iii) Double mutant = neither
(7/10)
(i) AAAA mutant = Receiver but not Activator
(ii) Kinase-dead mutant = Activator but not Receiver
(iii) Double mutant = neither
(7/10)
This work started by Yasushi Kondo solving an X-ray crystal structure of BRAF in complex with its substrate MEK1 where the BRAF dimeric interface was asymmetric, with the NtA motif of only one of the subunits making interface contacts. Yes, like in that beautiful model! (6/10)
October 14, 2025 at 8:17 AM
This work started by Yasushi Kondo solving an X-ray crystal structure of BRAF in complex with its substrate MEK1 where the BRAF dimeric interface was asymmetric, with the NtA motif of only one of the subunits making interface contacts. Yes, like in that beautiful model! (6/10)
However, to paraphrase the late Cyrus Chothia, if the data don't fit a beautiful model, you need more data. You can't just forget about the NtA - cancer genetics and the early Marais experiments don't allow it! (5/10)
October 14, 2025 at 8:17 AM
However, to paraphrase the late Cyrus Chothia, if the data don't fit a beautiful model, you need more data. You can't just forget about the NtA - cancer genetics and the early Marais experiments don't allow it! (5/10)
The problem? Multiple BRAF and CRAF structures were solved since, and … dimers were symmetric, kinases looked active, and the NtA looked disordered. (4/10)
October 14, 2025 at 8:17 AM
The problem? Multiple BRAF and CRAF structures were solved since, and … dimers were symmetric, kinases looked active, and the NtA looked disordered. (4/10)
15 years later, Susan Taylor et al proposed a model: Active RAFs are dimers and one subunit (the "Activator") uses its NtA to activate the other subunit (the "Receiver"). It is only the Receiver that takes the fully active kinase conformation. tinyurl.com/RAFmodel (3/10)
Allosteric Activation of Functionally Asymmetric RAF Kinase Dimers
Although RAF kinases are critical for controlling cell growth, their mechanism of activation is incompletely understood. Recently, dimerization was sh…
tinyurl.com
October 14, 2025 at 8:17 AM
15 years later, Susan Taylor et al proposed a model: Active RAFs are dimers and one subunit (the "Activator") uses its NtA to activate the other subunit (the "Receiver"). It is only the Receiver that takes the fully active kinase conformation. tinyurl.com/RAFmodel (3/10)
In 1999, Marais lab showed that this is because of the 4-residue N-terminal acidic (NtA) motif. In CRAF, the NtA must be phosphorylated to become acidic and the kinase to become active. In BRAF the NtA is already acidic, making BRAF one step closer to (over)active. tinyurl.com/NtAmotif (2/10)
Serine and tyrosine phosphorylations cooperate in Raf‐1, but not B‐Raf activation | The EMBO Journal
EMBO Press is an editorially independent publishing platform for the development of EMBO scientific publications.
tinyurl.com
October 14, 2025 at 8:17 AM
In 1999, Marais lab showed that this is because of the 4-residue N-terminal acidic (NtA) motif. In CRAF, the NtA must be phosphorylated to become acidic and the kinase to become active. In BRAF the NtA is already acidic, making BRAF one step closer to (over)active. tinyurl.com/NtAmotif (2/10)
Skeetorial on our BRAF preprint!
tinyurl.com/asymmBRAF
The RAS->RAF->MEK->ERK cascade carries mutations in most human cancers. Interestingly, although we have three RAF paralogues (A, B and C), it is the BRAF that is predominantly mutated in cancer patients. (1/10)
tinyurl.com/asymmBRAF
The RAS->RAF->MEK->ERK cascade carries mutations in most human cancers. Interestingly, although we have three RAF paralogues (A, B and C), it is the BRAF that is predominantly mutated in cancer patients. (1/10)
Mechanism of MEK1 phosphorylation by the N-terminal acidic motif-mediated asymmetric BRAF dimer
The RAF/MEK/ERK signaling cascade regulates cell proliferation and differentiation and is frequently dysregulated in cancer. Approximately 90% of RAF-mutant cancers harbour mutations in B-type of Rapi...
tinyurl.com
October 14, 2025 at 8:17 AM
Skeetorial on our BRAF preprint!
tinyurl.com/asymmBRAF
The RAS->RAF->MEK->ERK cascade carries mutations in most human cancers. Interestingly, although we have three RAF paralogues (A, B and C), it is the BRAF that is predominantly mutated in cancer patients. (1/10)
tinyurl.com/asymmBRAF
The RAS->RAF->MEK->ERK cascade carries mutations in most human cancers. Interestingly, although we have three RAF paralogues (A, B and C), it is the BRAF that is predominantly mutated in cancer patients. (1/10)
Reposted by Tina Perica
For every Nobel that goes to a criminally under-recognized woman scientist (Brunkow, Karikó), or fails to go (Candy Lee), a week of mourning and reform for an academic system wherein you can do Nobel-prize-worthy-work and still end up without a conceivable path to being a professor.
BREAKING: The Nobel Prize in Physiology or Medicine has been awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi "for their discoveries concerning peripheral immune tolerance"
Stay tuned for more.
#NobelPrize
Stay tuned for more.
#NobelPrize
October 6, 2025 at 10:13 AM
For every Nobel that goes to a criminally under-recognized woman scientist (Brunkow, Karikó), or fails to go (Candy Lee), a week of mourning and reform for an academic system wherein you can do Nobel-prize-worthy-work and still end up without a conceivable path to being a professor.
It’s the chicken or the egg question. We are only now realising this layer is important because it was so hard to study. And because of that, people studying it probably didn’t do well in their careers
October 3, 2025 at 9:30 AM
It’s the chicken or the egg question. We are only now realising this layer is important because it was so hard to study. And because of that, people studying it probably didn’t do well in their careers
Seems like they also listen to Ghost at Science!
Last year, a special issue of Science explored the complex and close associations #rats share with humans—from their ubiquity in the human environment to their crucial role as biomedical models.
🐀 Learn more: https://scim.ag/46VBOrb #ScienceMagArchives
🐀 Learn more: https://scim.ag/46VBOrb #ScienceMagArchives
September 29, 2025 at 2:46 PM
Seems like they also listen to Ghost at Science!